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Niu HG, Hu GK, Li T, Guo Z, Hu Y, Gong YK, Ye GQ, Chen DJ, An JL, Gao WS. Association of a Body Shape Index with Bone Mineral Density and Osteoporosis Among U.S. Adults: Evidence from NHANES. Calcif Tissue Int 2025; 116:76. [PMID: 40415018 DOI: 10.1007/s00223-025-01386-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 05/05/2025] [Indexed: 05/27/2025]
Abstract
Obesity significantly impacts bone health. The ABSI is an innovative metric for assessing obesity, offering greater accuracy than traditional measures such as body mass index and waist circumference in reflecting visceral fat accumulation. This study aims to investigate the relationship between ABSI and BMD as well as its association with osteoporosis among U.S. adults, utilizing data from the NHANES. This cross-sectional study analyzed data from adults aged 18 years and older, collected during the 2005-2006, 2013-2014, and 2017-2018 cycles of the NHANES. Multivariate linear regression models were used to evaluate the association between ABSI and BMD. Multivariate logistic regression models were applied to assess the relationship between ABSI and osteoporosis. Restricted cubic spline models were employed to evaluate potential nonlinear associations between ABSI and BMD as well as osteoporosis. Additionally, subgroup analyses and sensitivity analyses were conducted to ensure the robustness of the findings. A total of 5487 participants were included in the analysis, with a mean age of 47.04 years. ABSI was found to be negatively associated with BMD at the femoral neck, total femur, and lumbar spine. Participants in the highest ABSI quartile exhibited a significantly higher prevalence of osteoporosis compared to those in the lowest quartile (OR = 1.95; 95% CI 1.61-2.26). Nonlinear relationships were observed between ABSI and BMD at the femoral neck, total femur, lumbar spine, and osteoporosis, with inflection points at 8.84, 8.56, 9.23, and 8.14, respectively. Sensitivity analyses confirmed the robustness of these associations. Subgroup analyses revealed significant interactions between ABSI and BMD in smokers (P < 0.05). This study identifies a significant negative association between ABSI and BMD and a positive association with osteoporosis. The nonlinear relationship observed between ABSI and both BMD and osteoporosis underscores the importance of maintaining an optimal ABSI to promote bone health. These findings support the utility of ABSI as a valuable marker for early identification and prevention of osteoporosis, offering actionable insights for clinical and public health strategies. Future longitudinal research is warranted to validate these results and further elucidate the underlying mechanisms.
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Affiliation(s)
- He-Gang Niu
- Department of Orthopaedic Surgery, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000, Hebei Province, China
| | - Gao-Kai Hu
- Department of Orthopaedic Surgery, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000, Hebei Province, China
| | - Tong Li
- Department of Orthopaedic Surgery, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000, Hebei Province, China
| | - Zhao Guo
- Department of Orthopaedic Surgery, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000, Hebei Province, China
| | - Yang Hu
- Department of Orthopaedic Surgery, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000, Hebei Province, China
| | - Yu-Kang Gong
- Department of Orthopaedic Surgery, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000, Hebei Province, China
| | - Gao-Qi Ye
- Department of Orthopaedic Surgery, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000, Hebei Province, China
| | - De-Jin Chen
- Department of Orthopaedic Surgery, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000, Hebei Province, China
| | - Ji-Long An
- Department of Orthopaedic Surgery, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000, Hebei Province, China.
| | - Wen-Shan Gao
- Department of Orthopaedic Surgery, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000, Hebei Province, China.
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Klinaku FT, Comi L, Giglione C, Magni P. An integrated view of the pathophysiological crosstalk between adipose tissue, bone and cardiovascular system in men and women. J Endocrinol Invest 2025; 48:1061-1074. [PMID: 39692990 DOI: 10.1007/s40618-024-02516-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 12/07/2024] [Indexed: 12/19/2024]
Abstract
BACKGROUND Obesity, bone-related and cardiovascular diseases (CVD) are among the leading global health concerns. Growing evidence suggests that these conditions share common pathophysiological pathways and disease outcomes. PATHOGENETIC INTERACTIONS OF OBESITY, CVD AND BONE-RELATED DISEASES: Obesity is a well-established risk factor for atherosclerotic CVD (ASCVD), as dysfunctional ectopic adipose tissue may produce endocrine/paracrine hormones modulating metabolic processes and inflammation, predisposing to ASCVD. Although obesityhas been considered a protective factor for bone loss, it may lead to osteoporosis development and increased fracture risk at specific sites. Biological and epidemiological evidence has demonstrated the existence of a dynamic relationship between ASCVD and osteoporosis, since atherosclerotic calcification and bone mineralization share common pathophysiological mechanisms. Therefore, addressing ASCVD, obesity, and bone-related diseases requires multiple-level approach, which involve accurate screening, lifestyle modifications and pharmacological interventions.The current evidence about the pathophysiological relationships between obesity, bone-related diseases and ASCVD is discussed herein, highlighting common risk factors, proposed biomolecular mechanisms, clinical outcomes, lifestyle changes and pharmacological treatments. CONCLUSIONS As populations become increasingly older and obese, understanding the correlation within this triad highlights an unmet clinical need. Applying this knowledge would help to reduce both societal and individual costs, while supporting the development of novel preventive, diagnostic and therapeutic strategies to reduce morbidity and disability associated with cardio-metabolic and bone-related diseases.
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Affiliation(s)
- Fationa Tolaj Klinaku
- Department of Pharmacological and Biomolecular Sciences, Università Degli Studi Di Milano, 20133, Milan, Italy
| | - Laura Comi
- Department of Pharmacological and Biomolecular Sciences, Università Degli Studi Di Milano, 20133, Milan, Italy
| | - Claudia Giglione
- Department of Pharmacological and Biomolecular Sciences, Università Degli Studi Di Milano, 20133, Milan, Italy
| | - Paolo Magni
- Department of Pharmacological and Biomolecular Sciences, Università Degli Studi Di Milano, 20133, Milan, Italy.
- IRCCS MultiMedica, 20099, Sesto San Giovanni (Milan), Italy.
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Wu Q, Zhou J, Du D, Guo B, Wang H, Lv W. Mongolian medicine Sugemule-7 decoction prevents osteoporosis via Erk1/2 and p38 MAPK signaling pathways according to network pharmacology analysis. Int J Biol Macromol 2025; 292:139166. [PMID: 39743063 DOI: 10.1016/j.ijbiomac.2024.139166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 11/27/2024] [Accepted: 12/07/2024] [Indexed: 01/04/2025]
Abstract
Osteoporosis (OP) is a significant global public health concern that requires the development of safe and effective drugs for prevention and treatment. Sugemule-7 (SGML-7) decoction, a traditional Mongolian herbal prescription, has long been used for treating OP, but its components and mechanisms of action remain unclear. The study identified the main compounds of SGML-7 using UHPLC-Q Exactive MS and explored the multi-target mechanisms of SGML-7 in OP through network pharmacology and molecular docking. A retinoic acid (RA)-induced mouse OP model was utilized to confirm the therapeutic effects and potential mechanism of SGML-7. Additionally, mouse pre-osteoblastic (MC3T3-E1) cells treated with SGML-7 medicated serum were employed to delve deeper into the molecular mechanisms. The UHPLC-Q Exactive MS analysis, network pharmacology, and molecular docking suggested that the synergistic effect of multiple active compounds could be the main contributor to SGML-7 for its anti-OP activities. Moreover, MAPK1, JUN, ESR1, TP53, AKT1, NCOA1, FOS, and NR3C1 were identified as potential key targets, and the MAPK signaling pathway was among the signaling pathways possibly involved in the anti-OP activities of SGML-7. Consistent with these findings, experimental studies confirmed that SGML-7 prevented bone loss, enhanced bone quality in OP mice, and promoted osteoblastic activity and bone formation in MC3T3-E1 cells by modulating MAPK-associated targets. Taken together, SGML-7 shows promise as an effective and appealing anti-OP drug candidate.
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Affiliation(s)
- Qijin Wu
- Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
| | - Jing Zhou
- Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, Hebei 075131, China
| | - Donghua Du
- Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, Hebei 075131, China
| | - Bing Guo
- Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, Hebei 075131, China
| | - Haifeng Wang
- Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, Hebei 075131, China
| | - Wenting Lv
- Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, Hebei 075131, China.
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Farella I, Chiarito M, Vitale R, D’Amato G, Faienza MF. The "Burden" of Childhood Obesity on Bone Health: A Look at Prevention and Treatment. Nutrients 2025; 17:491. [PMID: 39940349 PMCID: PMC11821239 DOI: 10.3390/nu17030491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 01/26/2025] [Accepted: 01/27/2025] [Indexed: 02/16/2025] Open
Abstract
Childhood obesity represents a multifaceted challenge to bone health, influenced by a combination of endocrine, metabolic, and mechanical factors. Excess body fat correlates with an increase in bone mineral density (BMD) yet paradoxically elevates fracture risk due to compromised bone quality and increased mechanical loading on atypical sites. Additionally, subjects with syndromic obesity, as well as individuals with atypical nutritional patterns, including those with eating disorders, show bone fragility through unique genetic and hormonal dysregulations. Emerging evidence underscores the adverse effects of new pharmacological treatments for severe obesity on bone health. Novel drugs, such as glucagon-like peptide-1 (GLP-1) receptor agonists, and bariatric surgery demonstrate potential in achieving weight loss, though limited evidence is available regarding their short- and long-term impacts on skeletal health. This review provides a comprehensive analysis of the mechanisms underlying the impact of childhood obesity on bone health. It critically appraises evidence from in vitro studies, animal models, and clinical research in children with exogenous obesity, syndromic obesity, and eating disorders. It also explores the effects of emerging pharmacological and surgical treatments for severe obesity on skeletal integrity, highlights prevention strategies, and identifies research gaps.
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Affiliation(s)
- Ilaria Farella
- Department of Medicine and Surgery, LUM University, Casamassima, 70010 Bari, Italy;
| | - Mariangela Chiarito
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Rossella Vitale
- Giovanni XXIII Pediatric Hospital, University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Gabriele D’Amato
- Neonatal Intensive Care Unit, Di Venere Hospital, 70012 Bari, Italy;
| | - Maria Felicia Faienza
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari “Aldo Moro”, 70124 Bari, Italy;
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An F, Jia X, Shi Y, Xiao X, Yang F, Su J, Peng X, Geng G, Yan C. The ultimate microbial composition for correcting Th17/Treg cell imbalance and lipid metabolism disorders in osteoporosis. Int Immunopharmacol 2025; 144:113613. [PMID: 39571271 DOI: 10.1016/j.intimp.2024.113613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 10/28/2024] [Accepted: 11/07/2024] [Indexed: 12/15/2024]
Abstract
Osteoporosis is a systemic bone disease characterised by decreased bone mass and a deteriorated bone microstructure, leading to increased bone fragility and fracture risk. Disorders of the intestinal microbiota may be key inducers of osteoporosis. Furthermore, such disorders may contribute to osteoporosis by influencing immune function and lipid metabolism. Therefore, in this review, we aimed to summarise the molecular mechanisms through which the intestinal microbiota affect the onset and development of osteoporosis by regulating Th17/Treg imbalance and lipid metabolism disorders. We also discussed the regulatory mechanisms underlying the effect of intestinal microbiota-related modulators on Th17/Treg imbalance and lipid metabolism disorders in osteoporosis, to explore new molecular targets for its treatment and provide a theoretical basis for clinical management.
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Affiliation(s)
- Fangyu An
- Teaching Experiment Training Center, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China.
| | - Xueru Jia
- School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Yangyang Shi
- School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Xiaolong Xiao
- School of Tradional Chinese and Werstern Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Fan Yang
- School of Tradional Chinese and Werstern Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Junchang Su
- School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Xia Peng
- School of Tradional Chinese and Werstern Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Guangqin Geng
- School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China
| | - Chunlu Yan
- School of Tradional Chinese and Werstern Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China.
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Fornari Laurindo L, Minniti G, Rodrigues VD, Fornari Laurindo L, Strozze Catharin VMC, Baisi Chagas EF, Dos Anjos VD, de Castro MVM, Baldi Júnior E, Ferraroni Sanches RC, Mendez-Sanchez N, Maria Barbalho S. Exploring the Logic and Conducting a Comprehensive Evaluation of the Adiponectin Receptor Agonists AdipoRon and AdipoAI's Impacts on Bone Metabolism and Repair-A Systematic Review. Curr Med Chem 2025; 32:1168-1194. [PMID: 39206478 DOI: 10.2174/0109298673308301240821052742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 05/17/2024] [Accepted: 07/05/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION Adiponectin replacement therapy shows promising outcomes in various diseases, especially for bone-related disorders. Challenges in using the complete protein have led to alternative approaches, with AdipoRon and AdipoAI emerging as extensively researched drug candidates. Their influence on models of bone-related disorders has progressed considerably but there has been no review of their effectiveness in modulating bone metabolism and repair. METHODS This systematic review seeks to address this knowledge gap. Based on preclinical evidence from PubMed, EMBASE, and COCHRANE, ten studies were included following PRISMA guidelines. The JBI Checklist Critical Appraisal Tool assessed the quality of this systematic review. The studies encompassed various animal models, addressing bone defects, osseointegration, diabetes-associated periodontitis, fracture repair, growth retardation, and diabetes-associated peri-implantitis. RESULTS AdipoRon and AdipoAI demonstrated effectiveness in modulating bone metabolism and repair through diverse pathways, including the activation of AdipoR1/APPL1, inhibition of F-actin ring formation, suppression of IκB-α phosphorylation, p65 nuclear translocation and Wnt5a-Ror2 signaling pathway, reduction of CCL2 secretion and expression, regulation of autophagy via LC3A/B expression, modulation of SDF-1 production, activation of the ERK1/2 signaling pathway, modulation of bone integration-related markers and osteokines such as RANKL, BMP-2, OPG, OPN, and Runx2, inhibition of RANKL in osteoblasts, and inhibition of podosome formation via the activation of AMPK. CONCLUSION While preclinical studies show promise, human trials are crucial to confirm the clinical safety and effectiveness of AdipoRon and AdipoAI. Caution is necessary due to potential off-target effects, especially in bone therapy with multi-target approaches. Structural biology and computational methods can help predict and understand these effects.
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Affiliation(s)
- Lucas Fornari Laurindo
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, São Paulo, Brazil
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Giulia Minniti
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Victoria Dogani Rodrigues
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, São Paulo, Brazil
| | - Lívia Fornari Laurindo
- Medical Department, School of Medicine, Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto 15090-000, São Paulo, Brazil
| | - Virginia Maria Cavallari Strozze Catharin
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Eduardo Federighi Baisi Chagas
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Vinicius Dias Dos Anjos
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Marcela Vialogo Marques de Castro
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Edgar Baldi Júnior
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Raquel Cristina Ferraroni Sanches
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Nahum Mendez-Sanchez
- Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico
| | - Sandra Maria Barbalho
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
- Department of Biochemistry and Nutrition, School of Food and Technology of Marília (FATEC), Marília 17500-000, São Paulo, Brazil
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Nielsen BU, Mikkelsen CR, Oturai PS, Krogh-Madsen R, Katzenstein TL, Ritz C, Pressler T, Almdal TP, Mathiesen IHM, Faurholt-Jepsen D. A cross-sectional study in adiponectin, glucose metabolism, and body composition in cystic fibrosis. Front Endocrinol (Lausanne) 2024; 15:1382241. [PMID: 39530118 PMCID: PMC11550925 DOI: 10.3389/fendo.2024.1382241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 10/07/2024] [Indexed: 11/16/2024] Open
Abstract
Objective We hypothesized that the insulin-sensitizing adipokine adiponectin (ADP) is upregulated in cystic fibrosis (CF) related diabetes (CFRD) and underweight adults with CF. We aimed to assess correlations between glucose metabolism, body composition and ADP in CF. Methods We performed a cross-sectional study among adults with CF at the Copenhagen CF Center. The study included a fasting level of ADP, an oral glucose tolerance test (OGTT), and a dual energy-x-ray absorptiometry scan. Results In total, 115 patients were included of whom 104 had an OGTT performed. Glucose intolerance was not correlated with ADP in multivariable analysis, while increased hepatic insulin resistance (i.e., HOMA-IR) was correlated with reduced ADP levels. ADP declined by 4% (eβ 0.96, 95% CI: 0.94, 0.98), 5% (eβ 0.95, 95% CI: 0.93, 0.98), 9% (eβ 0.91, 95% CI: 0.87, 0.95), and 83% (eβ 0.17, 95% CI: 0.08, 0.37) for each one unit (kg/m2) increase in body mass index, fat mass index, muscle mass index, and bone mineral content index, respectively. Conclusions In CF, ADP was negatively correlated with hepatic insulin resistance as well as low fat, muscle, and bone mass, but not with glucose intolerance. This suggests that malnutrition leads to higher ADP levels in CF.
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Affiliation(s)
- Bibi Uhre Nielsen
- Cystic Fibrosis Center Copenhagen, Department of Infectious Diseases, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
| | - Christine Råberg Mikkelsen
- Cystic Fibrosis Center Copenhagen, Department of Infectious Diseases, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
| | - Peter Sandor Oturai
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
| | - Rikke Krogh-Madsen
- Centre for Physical Activity Research, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
- Department of Infectious Diseases, Copenhagen University Hospital – Hvidovre, Copenhagen, Denmark
| | - Terese Lea Katzenstein
- Cystic Fibrosis Center Copenhagen, Department of Infectious Diseases, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
| | - Christian Ritz
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
| | - Tacjana Pressler
- Cystic Fibrosis Center Copenhagen, Department of Infectious Diseases, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
| | - Thomas Peter Almdal
- Department of Endocrinology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
| | - Inger Hee Mabuza Mathiesen
- Cystic Fibrosis Center Copenhagen, Department of Infectious Diseases, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
| | - Daniel Faurholt-Jepsen
- Cystic Fibrosis Center Copenhagen, Department of Infectious Diseases, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
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Liao S, Shang J, Cheng L, Zhu J, Huang F. A higher body mass index and increased syndesmophytes volume are associated with facet joints ankylosis on thoracic spine in patients with ankylosing spondylitis: a retrospective cohort study. BMC Rheumatol 2024; 8:44. [PMID: 39300556 PMCID: PMC11411733 DOI: 10.1186/s41927-024-00408-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 08/16/2024] [Indexed: 09/22/2024] Open
Abstract
OBJECTIVE To investigate the association between syndesmophytes and facet joint (FJ) lesions in patients with ankylosing spondylitis (AS), and to identify clinical factors associated with FJ ankylosis (FJA) in thoracic segment. METHODS Ninety-seven patients with AS who underwent thoracic spine computed tomography (CT) or chest CT and without completely thoracic spine fusion were included. FJ lesions were analyzed for the numbers and distribution of normal, ankylosis, erosions, joint-space narrowing, osteophytes, and subchondral sclerosis. The volume of vertebral syndesmophtes unit (VSU) and total thoracic syndesmophtes volume were separately calculated by Mimics software. Clinical factors associated with FJA were investigated using generalized estimation equation (GEE). The association between syndesmophtes volume and numbers of FJ structural lesions was analyzed using generalized additive mixed model (GAMM). RESULTS 2328 FJ and 1164 VSUs in thoracic spine were assessed. The majority FJ structural lesions were ankylosis (32.39%). FJA was more frequently seen in vertebrae with syndesmophytes formation (p < 0.001). GEE showed that patients with normal BMI (18.5-24.9 kg/m2) and high BMI (> 24.9 kg/m2) were more likely to have FJA in thoracic spine (odds rations [95% confidence interval]: 0.27(0.12-0.59), 1.45(1.03-8.57), respectively). GAMM showed that syndesmophytes volume increase the numbers of FJA (standard β = 0.009, p < 0.05) and decreased the numbers of normal FJ (standard β = -0.07, p < 0.01). CONCLUSION FJA was the most common FJ structural lesion in thoracic spine, and it increases linearly with syndesmophytes before the bridging syndesmophytes formed. A higher BMI (especially > 24.9 kg/m2) and increased syndesmophytes volume are associated with FJA in thoracic spine.
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Affiliation(s)
- Simin Liao
- Department of Rheumatology and Immunology, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jian Shang
- Department of Rheumatology and Endocrinology, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Liuquan Cheng
- Department of Radiology, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jian Zhu
- Department of Rheumatology and Immunology, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
| | - Feng Huang
- Department of Rheumatology and Immunology, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
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Yang X, Fan Y, Liang J, Cao R, Zhang B, Li J, Li Z, He S, Liu N, Du J, Hu Y. Polyaptamer-Driven Crystallization of Alendronate for Synergistic Osteoporosis Treatment through Osteoclastic Inhibition and Osteogenic Promotion. ACS NANO 2024; 18:22431-22443. [PMID: 39103298 DOI: 10.1021/acsnano.4c07265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/07/2024]
Abstract
Osteoclastic inhibition using antiresorptive bisphosphonates and osteogenic promotion using antisclerostin agents represent two distinct osteoporosis treatments in clinical practice, each individual treatment suffers from unsatisfactory therapeutic efficacy due to its indirect intervention in osteoclasis and promotion of osteogenesis simultaneously. Although this issue is anticipated to be resolved by drug synergism, a tempting carrier-free dual-medication nanoassembly remains elusive. Herein, we prepare such a nanoassembly made of antiresorptive alendronate (ALN) crystal and antisclerostin polyaptamer (Apt) via a nucleic acid-driven crystallization method. This nanoparticle can protect Apt from rapid nuclease degradation, avoid the high cytotoxicity of free ALN, and effectively concentrate in the cancellous bone by virtue of the bone-binding ability of DNA and ALN. More importantly, the acid microenvironment of cancellous bone triggers the disassociation of nanoparticles for sustained drug release, from which ALN inhibits the osteoclast-mediated bone resorption while Apt promotes osteogenic differentiation. Our work represents a pioneering demonstration of nucleic acid-driven crystallization of a bisphosphonate into a tempting carrier-free dual-medication nanoassembly. This inaugural advancement augments the antiosteoporosis efficacy through direct inhibition of osteoclasis and promotion of osteogenesis simultaneously and establishes a paradigm for profound understanding of the underlying synergistic antiosteoporosis mechanism of antiresorptive and antisclerostin components. It is envisioned that this study provides a highly generalizable strategy applicable to the tailoring of a diverse array of DNA-inorganic nanocomposites for targeted regulation of intricate pathological niches.
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Affiliation(s)
- Xingsen Yang
- Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, P. R. China
| | - Yu Fan
- Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, P. R. China
| | - Junhao Liang
- Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, P. R. China
- Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China
- Department of Gynaecology and Obstetrics, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, P. R. China
| | - Runfeng Cao
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, P. R. China
| | - Beibei Zhang
- Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, P. R. China
| | - Jianhua Li
- Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, P. R. China
| | - Zejuan Li
- Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, P. R. China
| | - Shisheng He
- Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China
| | - Na Liu
- 2nd Physics Institute, University of Stuttgart, Stuttgart D-70569, Germany
- Max Planck Institute for Solid State Research, Stuttgart D-70569, Germany
| | - Jianzhong Du
- Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, P. R. China
- Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P. R. China
- Department of Gynaecology and Obstetrics, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, P. R. China
| | - Yong Hu
- Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, P. R. China
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10
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Pan R, Wang R, Zhang Y, Ji H, Liang X, Zhao Y. The association of waist circumference with bone mineral density and risk of osteoporosis in US adult: National health and nutrition examination survey. Bone 2024; 185:117134. [PMID: 38821388 DOI: 10.1016/j.bone.2024.117134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 05/07/2024] [Accepted: 05/23/2024] [Indexed: 06/02/2024]
Abstract
PURPOSE Obesity and osteoporosis (OP) are receiving increasing attention. Waist circumference (WC) is an effective indicator for assessing central obesity. Currently, there is controversy regarding the relationship between WC and bone mineral density (BMD), as well as OP. Therefore, our study aims to utilize data from the National Health and Nutrition Examination Survey (NHANES) to evaluate the relationship between WC and BMD, as well as OP, in US adults. METHODS This cross-sectional study included subjects aged ≥18 years from the NHANES 1999-2018. Multivariate linear regression models were performed to investigate the association between WC and BMD. Multivariate logistic regression models were employed to assess the relationship between WC and OP. Restricted cubic spline curves were used to assess potential nonlinear association between WC and BMD, OP. Subgroup analysis and sensitivity analysis were performed to assess the robustness of the results. RESULTS Finally, 11,165 participants (non-OP, n = 10,465; OP, n = 700) were included in the final analysis. The results showed that WC was positively associated with total femur (TF), femoral neck (FN), and lumbar spine (LS) BMD, and might be a protective factor for OP, independent of traditional confounding factors. For each 1 cm increased in WC, TF BMD, FN BMD and LS BMD increased by 0.004 g/cm2, 0.003 g/cm2 and 0.003 g/cm2, respectively, and the risk of OP decreased by 3.1 %. Furthermore, there was a non-linear relationship between WC and BMD, OP. The association remained robust in sensitivity and subgroup analyses. CONCLUSION In US adults, there is a positive association between WC and BMD, and WC may be a protective factor for the risk of OP. The association between WC and BMD as well as OP exhibits a non-linear relationship.
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Affiliation(s)
- Runzhou Pan
- Department of Endocrinology, Cangzhou Central Hospital, Cangzhou, Hebei Province, China.
| | - Rongrong Wang
- Department of Endocrinology, Cangzhou Central Hospital, Cangzhou, Hebei Province, China
| | - Yan Zhang
- Department of Endocrinology, Cangzhou Central Hospital, Cangzhou, Hebei Province, China
| | - Hong Ji
- Department of Endocrinology, Cangzhou Central Hospital, Cangzhou, Hebei Province, China
| | - Xue Liang
- Department of Endocrinology, Cangzhou Central Hospital, Cangzhou, Hebei Province, China
| | - Yongcai Zhao
- Department of Endocrinology, Cangzhou Central Hospital, Cangzhou, Hebei Province, China
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11
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Pechmann LM, Pinheiro FI, Andrade VFC, Moreira CA. The multiple actions of dipeptidyl peptidase 4 (DPP-4) and its pharmacological inhibition on bone metabolism: a review. Diabetol Metab Syndr 2024; 16:175. [PMID: 39054499 PMCID: PMC11270814 DOI: 10.1186/s13098-024-01412-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 07/10/2024] [Indexed: 07/27/2024] Open
Abstract
BACKGROUND Dipeptidyl peptidase 4 (DPP-4) plays a crucial role in breaking down various substrates. It also has effects on the insulin signaling pathway, contributing to insulin resistance, and involvement in inflammatory processes like obesity and type 2 diabetes mellitus. Emerging effects of DPP-4 on bone metabolism include an inverse relationship between DPP-4 activity levels and bone mineral density, along with an increased risk of fractures. MAIN BODY The influence of DPP-4 on bone metabolism occurs through two axes. The entero-endocrine-osseous axis involves gastrointestinal substrates for DPP-4, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). Studies suggest that supraphysiological doses of exogenous GLP-2 has a significant inhibitory effect on bone resorption, however the specific mechanism by which GLP-2 influences bone metabolism remains unknown. Of these, GIP stands out for its role in bone formation. Other gastrointestinal DPP-4 substrates are pancreatic peptide YY and neuropeptide Y-both bind to the same receptors and appear to increase bone resorption and decrease bone formation. Adipokines (e.g., leptin and adiponectin) are regulated by DPP-4 and may influence bone remodeling and energy metabolism in a paracrine manner. The pancreatic-endocrine-osseous axis involves a potential link between DPP-4, bone, and energy metabolism through the receptor activator of nuclear factor kappa B ligand (RANKL), which induces DPP-4 expression in osteoclasts, leading to decreased GLP-1 levels and increased blood glucose levels. Inhibitors of DPP-4 participate in the pancreatic-endocrine-osseous axis by increasing endogenous GLP-1. In addition to their glycemic effects, DPP-4 inhibitors have the potential to decrease bone resorption, increase bone formation, and reduce the incidence of osteoporosis and fractures. Still, many questions on the interactions between DPP-4 and bone remain unanswered, particularly regarding the effects of DPP-4 inhibition on the skeleton of older individuals. CONCLUSION The elucidation of the intricate interactions and impact of DPP-4 on bone is paramount for a proper understanding of the body's mechanisms in regulating bone homeostasis and responses to internal stimuli. This understanding bears significant implications in the investigation of conditions like osteoporosis, in which disruptions to these signaling pathways occur. Further research is essential to uncover the full extent of DPP-4's effects on bone metabolism and energy regulation, paving the way for novel therapeutic interventions targeting these pathways, particularly in older individuals.
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Affiliation(s)
- L M Pechmann
- Universidade Federal do Paraná, Setor de Ciências da Saúde, Endocrine Division (SEMPR), Centro de Diabetes Curitiba, Academic Research Center Pro Renal Institute, Curitiba, Brazil.
| | - F I Pinheiro
- Biotechnology at Universidade Potiguar and Discipline of Ophthalmology at the Federal University of Rio Grande do Norte (UFRN), Natal, Brazil
| | - V F C Andrade
- Academic Research Center Pro Renal Institute, Endocrine Division, Hospital de Cínicas da Universidade Federal do Paraná (SEMPR), Curitiba, Brazil
| | - C A Moreira
- Academic Research Center Pro Renal Institute, Endocrine Division, Hospital de Clinicas da Universidade Federal do Paraná ( SEMPR), Curitiba, Brazil
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12
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Niu H, Zhou M, Xu X, Xu X. Bone Marrow Adipose Tissue as a Critical Regulator of Postmenopausal Osteoporosis - A Concise Review. Clin Interv Aging 2024; 19:1259-1272. [PMID: 39011312 PMCID: PMC11249116 DOI: 10.2147/cia.s466446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 06/27/2024] [Indexed: 07/17/2024] Open
Abstract
Postmenopausal osteoporosis (PMOP) is a major health problem affecting millions of women worldwide. PMOP patients are often accompanied by abnormal accumulation of bone marrow adipose tissue (BMAT). BMAT is a critical regulator of bone homeostasis, and an increasing BMAT volume is negatively associated with bone mass reduction or fracture. BMAT regulates bone metabolism via adipokines, cytokines and the immune system, but the specific mechanisms are largely unknown. This review emphasizes the impact of estrogen deficiency on bone homeostasis and BMAT expansion, and the mechanism by which BMAT regulates PMOP, providing a promising strategy for targeting BMAT in preventing and treating PMOP.
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Affiliation(s)
- Huifang Niu
- Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
- Key Laboratory of Environment Correlative Dietology (Ministry of Education), Hubei Key Laboratory of Fruit Vegetable Processing Quality Control (Huazhong Agricultural University), School of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China
| | - Minfeng Zhou
- Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Xiaoyun Xu
- Key Laboratory of Environment Correlative Dietology (Ministry of Education), Hubei Key Laboratory of Fruit Vegetable Processing Quality Control (Huazhong Agricultural University), School of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China
| | - Xiaojuan Xu
- Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
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13
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Li J, Wu J, Xie Y, Yu X. Bone marrow adipocytes and lung cancer bone metastasis: unraveling the role of adipokines in the tumor microenvironment. Front Oncol 2024; 14:1360471. [PMID: 38571500 PMCID: PMC10987778 DOI: 10.3389/fonc.2024.1360471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 03/08/2024] [Indexed: 04/05/2024] Open
Abstract
Bone is a common site of metastasis for lung cancer. The "seed and soil" hypothesis suggests that the bone marrow microenvironment ("soil") may provide a conducive survival environment for metastasizing tumor cells ("seeds"). The bone marrow microenvironment, comprising a complex array of cells, includes bone marrow adipocytes (BMAs), which constitute about 70% of the adult bone marrow volume and may play a significant role in tumor bone metastasis. BMAs can directly provide energy for tumor cells, promoting their proliferation and migration. Furthermore, BMAs participate in the tumor microenvironment's osteogenesis regulation, osteoclast(OC) regulation, and immune response through the secretion of adipokines, cytokines, and inflammatory factors. However, the precise mechanisms of BMAs in lung cancer bone metastasis remain largely unclear. This review primarily explores the role of BMAs and their secreted adipokines (leptin, adiponectin, Nesfatin-1, Resistin, chemerin, visfatin) in lung cancer bone metastasis, aiming to provide new insights into the mechanisms and clinical treatment of lung cancer bone metastasis.
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Affiliation(s)
- Jian Li
- Laboratory of Endocrinology and Metabolism/Department of Endocrinology and Metabolism, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, China
- Department of Endocrinology and Metabolism, Shandong Second Provincial General Hospital, Jinan, China
| | - Jialu Wu
- Laboratory of Endocrinology and Metabolism/Department of Endocrinology and Metabolism, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yanni Xie
- Laboratory of Endocrinology and Metabolism/Department of Endocrinology and Metabolism, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xijie Yu
- Laboratory of Endocrinology and Metabolism/Department of Endocrinology and Metabolism, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, China
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14
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Guan J, Liu T, Chen H, Yang K. Association of type 2 Diabetes Mellitus and bone mineral density: a two-sample Mendelian randomization study. BMC Musculoskelet Disord 2024; 25:130. [PMID: 38347501 PMCID: PMC10860277 DOI: 10.1186/s12891-024-07195-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Accepted: 01/10/2024] [Indexed: 02/15/2024] Open
Abstract
BACKGROUND Observational studies have suggested that type 2 Diabetes Mellitus (DM2) is a potentially modifiable risk factor for lower BMD, but the causal relationship is unclear. This study aimed to examine whether the association of DM2 with lower BMD levels was causal by using Mendelian randomization (MR) analyses. METHODS We collected genome-wide association study data for DM2 and BMD of total body and different skeletal sites from the IEU database. Subsequently, we performed a two-sample Mendelian randomization analysis using the Two Sample MR package. RESULTS We identified a positive association between DM2 risk (61,714 DM2 cases and 596,424 controls) and total BMD, and other skeletal sites BMD, such as femoral neck BMD, ultra-distal forearm BMD and heel BMD. However, non-significant trends were observed for the effects of DM2 on lumbar-spine BMD. CONCLUSION In two-sample MR analyses, there was positive causal relationship between DM2 and BMD in both overall samples. In summary, while observational analyses consistently indicate a strong association between DM2 and low BMD, our MR analysis introduces a nuanced perspective. Contrary to the robust association observed in observational studies, our MR analysis suggests a significant link between DM2 and elevated BMD.
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Affiliation(s)
- Jianbin Guan
- Honghui-hospital, Xi'an Jiaotong University, Xi'an, 710054, China
- Shannxi Key Laboratory of Spine Bionic Treatment, Xi'an, China
| | - Tao Liu
- Honghui-hospital, Xi'an Jiaotong University, Xi'an, 710054, China
- Shannxi Key Laboratory of Spine Bionic Treatment, Xi'an, China
| | - Hao Chen
- Honghui-hospital, Xi'an Jiaotong University, Xi'an, 710054, China
- Shannxi Key Laboratory of Spine Bionic Treatment, Xi'an, China
| | - Kaitan Yang
- Honghui-hospital, Xi'an Jiaotong University, Xi'an, 710054, China.
- Shannxi Key Laboratory of Spine Bionic Treatment, Xi'an, China.
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15
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Kim TY, Schafer AL. Bariatric surgery, vitamin D, and bone loss. FELDMAN AND PIKE'S VITAMIN D 2024:161-184. [DOI: 10.1016/b978-0-323-91338-6.00009-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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16
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Hu K, Deya Edelen E, Zhuo W, Khan A, Orbegoso J, Greenfield L, Rahi B, Griffin M, Ilich JZ, Kelly OJ. Understanding the Consequences of Fatty Bone and Fatty Muscle: How the Osteosarcopenic Adiposity Phenotype Uncovers the Deterioration of Body Composition. Metabolites 2023; 13:1056. [PMID: 37887382 PMCID: PMC10608812 DOI: 10.3390/metabo13101056] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/26/2023] [Accepted: 10/04/2023] [Indexed: 10/28/2023] Open
Abstract
Adiposity is central to aging and several chronic diseases. Adiposity encompasses not just the excess adipose tissue but also body fat redistribution, fat infiltration, hypertrophy of adipocytes, and the shifting of mesenchymal stem cell commitment to adipogenesis. Bone marrow adipose tissue expansion, inflammatory adipokines, and adipocyte-derived extracellular vesicles are central to the development of osteopenic adiposity. Adipose tissue infiltration and local adipogenesis within the muscle are critical in developing sarcopenic adiposity and subsequent poorer functional outcomes. Ultimately, osteosarcopenic adiposity syndrome is the result of all the processes noted above: fat infiltration and adipocyte expansion and redistribution within the bone, muscle, and adipose tissues, resulting in bone loss, muscle mass/strength loss, deteriorated adipose tissue, and subsequent functional decline. Increased fat tissue, typically referred to as obesity and expressed by body mass index (the latter often used inadequately), is now occurring in younger age groups, suggesting people will live longer with the negative effects of adiposity. This review discusses the role of adiposity in the deterioration of bone and muscle, as well as adipose tissue itself. It reveals how considering and including adiposity in the definition and diagnosis of osteopenic adiposity, sarcopenic adiposity, and osteosarcopenic adiposity will help in better understanding the pathophysiology of each and accelerate possible therapies and prevention approaches for both relatively healthy individuals or those with chronic disease.
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Affiliation(s)
- Kelsey Hu
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Elizabeth Deya Edelen
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Wenqing Zhuo
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Aliya Khan
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Josselyne Orbegoso
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Lindsey Greenfield
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Berna Rahi
- Department of Human Sciences, Sam Houston State University College of Health Sciences, Huntsville, TX 77341, USA;
| | - Michael Griffin
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Jasminka Z. Ilich
- Institute for Successful Longevity, Florida State University, Tallahassee, FL 32304, USA;
| | - Owen J. Kelly
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
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17
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Zhao H, Shi D, Wang G, Ruan Y, Feng X, Jia C, Wang Q, Dong X. High-normal free thyroxine level is related with decreased bone mineral density in nonobese male patients with type 2 diabetes over 50 years old. Ther Adv Chronic Dis 2023; 14:20406223231195627. [PMID: 37664176 PMCID: PMC10472831 DOI: 10.1177/20406223231195627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 07/21/2023] [Indexed: 09/05/2023] Open
Abstract
Background The prevalence of 'low bone mineral density (BMD)' in Type 2 diabetes (T2DM), especially stratified by body mass index, is seldom reported. The relation of the euthyroid range and low BMD in T2DM remains to be further elucidated. Objectives We aim to investigate the thyroid hormones' impact on BMD among euthyroid patients with T2DM. Design and methods A total of 1452 hospitalized T2DM patients with normal thyroid function (43.6% males aged over 50 and 56.4% postmenopausal females) were enrolled in this cross-sectional study. BMD was measured at lumbar spine by GE lunar dual-energy X-ray absorptiometry system, and 'low BMD' was defined as T-score <-1.0 SD. The prevalence of 'low BMD' was compared between obese and nonobese (body mass index < 25 kg/m2) groups for both sexes, and the relation of low BMD and free T4 quartiles was explored by multiple logistic regression. Results The general prevalence of 'low BMD' was 12.3% for male patients aged over 50 (15.5% in the nonobese group and 8.0% in the obese group) and 49.8% for postmenopausal females (56.7% in the nonobese group and 48.9% in the obese group). After adjustment in multiple linear regression, free T4 level remained significantly related to decreased BMD in nonobese male subgroup. Multiple logistic regression revealed that BMD of the highest free T4 quartile (1.12-1.48 ng/dL) decreased significantly than other three quartiles after adjusting for confounding factors including age, body mass index, serum calcium and creatinine level, fasting glucose, alkaline phosphatase, glycosylated hemoglobin, total cholesterol, and smoking history (OR = 2.724, 95% CI = 1.085-6.840, p = 0.033). No significant relation was found in obese male or postmenopausal female groups. Conclusion High-normal free T4 is a potential independent risk factor for 'low BMD' in nonobese male T2DM patients aged over 50. Close attention should be paid to thyroid function profile, even within normal range, in nonobese men with underlying higher fracture risks on diabetes status.
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Affiliation(s)
- Hanxin Zhao
- Department of Endocrinology and Metabolism, Zhejiang University Affiliated Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, P.R. China
| | - Dike Shi
- Department of Gastrointestinal Surgery, Zhejiang University Second Affiliated Hospital, School of Medicine, Hangzhou, P.R. China
| | - Guoxing Wang
- Department of Endocrinology and Metabolism, Zhejiang University Affiliated Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, P.R. China
| | - Yu Ruan
- Department of Endocrinology and Metabolism, Zhejiang University Affiliated Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, P.R. China
| | - Xiaocheng Feng
- Department of Endocrinology and Metabolism, Zhejiang University Affiliated Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, P.R. China
| | - ChengFang Jia
- Department of Endocrinology and Metabolism, Zhejiang University Affiliated Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, P.R. China
| | - Qingqing Wang
- Department of Endocrinology and Metabolism, Zhejiang University Affiliated Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, P.R. China
| | - Xuehong Dong
- Department of Endocrinology and Metabolism, Zhejiang University Affiliated Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, P.R. China
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Wang W, Gu X, Cao Z, Wang X, Lei Y, Xu X, Wang S, Wu T, Bao Z. A potential correlation between adipokines, skeletal muscle function and bone mineral density in middle-aged and elderly individuals. Lipids Health Dis 2023; 22:111. [PMID: 37525169 PMCID: PMC10388529 DOI: 10.1186/s12944-023-01879-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 07/21/2023] [Indexed: 08/02/2023] Open
Abstract
BACKGROUND Evidence exists of a strong association between inflammation and a decrease in skeletal muscle function and bone mineral density (BMD); however, the specific mechanisms of these associations remain unclear. Adipokines, as key regulators of the inflammatory response, may be implicated in these processes. The objective of this study was to explore the potential correlation between adipokines, skeletal muscle function and BMD in middle-aged and elderly individuals. METHODS A comparative cross-sectional study was carried out at the Huadong Hospital Affiliated with Fudan University (Shanghai, China). A total of 460 middle-aged and elderly individuals were recruited, and 125 were enrolled in the analysis. Their biochemical indices, body composition, skeletal muscle function and BMD were measured. Bioinformatic analysis was also employed to identify potential adipokine targets linked to skeletal muscle function and BMD. To validate these targets, plasma and peripheral blood mononuclear cells (PBMCs) were harvested from these individuals and subjected to western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). RESULTS Individuals in this cross-sectional study were categorized into 2 groups according to their median skeletal muscle mass (SMM) (28.8 kg for males and 20.6 kg for females). Individuals with lower SMM exhibited poorer grip strength (P = 0.017), longer 5-Times-Sit-to-Stand Test (FTSST) duration (P = 0.029), lower total hip BMD (P = 0.043), lower femoral neck BMD (P = 0.011) and higher levels of inflammatory markers in comparison with individuals with higher SMM. Bioinformatics analysis identified LEP, ADIPOQ, RBP4, and DPP4 as potential adipokine targets associated with skeletal muscle function and BMD. In vitro experiments demonstrated that individuals with decreased skeletal muscle function and BMD expressed higher levels of these adipokines. CONCLUSIONS Skeletal muscle function is positively correlated with BMD and negatively correlated with levels of inflammatory markers among middle-aged and elderly individuals. Those with lower skeletal muscle function and BMD tend to have a higher expression of LEP, ADIPOQ, RBP4 and DPP4.
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Affiliation(s)
- Wenhao Wang
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, No 221 West Yan-An Road, Shanghai, 200040, China
| | - Xuchao Gu
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, No 221 West Yan-An Road, Shanghai, 200040, China
| | - Ziyi Cao
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China
- Department of Gastroenterology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China
| | - Xiaojun Wang
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China
- Department of Gerontology, Huadong Hospital Affiliated to Fudan University, No 221 West Yan-An Road, Shanghai, 200040, China
| | - Yiming Lei
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, No 221 West Yan-An Road, Shanghai, 200040, China
| | - Xiaoli Xu
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, No 221 West Yan-An Road, Shanghai, 200040, China
| | - Shiwen Wang
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China.
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, No 221 West Yan-An Road, Shanghai, 200040, China.
| | - Tao Wu
- Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, No 221 West Yan-An Road, Shanghai, 200040, China.
| | - Zhijun Bao
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China.
- Department of Gerontology, Huadong Hospital Affiliated to Fudan University, No 221 West Yan-An Road, Shanghai, 200040, China.
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Lin Y, Zhong X, Lu D, Yao W, Zhou J, Wu R, Feng F. Association of visceral and subcutaneous fat with bone mineral density in US adults: a cross-sectional study. Sci Rep 2023; 13:10682. [PMID: 37393338 PMCID: PMC10314932 DOI: 10.1038/s41598-023-37892-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 06/29/2023] [Indexed: 07/03/2023] Open
Abstract
The relationship between the accumulation of fat in visceral or subcutaneous tissue and bone mineral density (BMD) remains unclear. Our primary objective in this study was to illuminate this relationship by conducting an investigation on a vast scale, encompassing a nationally representative population in the United States. A weighted multiple linear regression model was established to evaluate the relationship between visceral fat, subcutaneous fat, and BMD. Additionally, the exploration of the potential nonlinear relationship was conducted employing the methodology of smooth curve fitting. In order to determine potential inflection points, a two-stage linear regression model was utilized. A total of 10,455 participants between the ages of 20 and 59 were included in this study. Various weighted multiple linear regression models revealed a negative correlation between lumbar BMD and visceral mass index (VMI) and subcutaneous mass index (SMI). However, the association between VMI and lumbar BMD displayed a U-shaped pattern upon employing the smooth curve fitting, and the inflection point of 0.304 kg/m2was determined using a two-stage linear regression model. Our findings indicated a negative association between subcutaneous fat and BMD. A U-shaped relationship was observed between visceral fat and BMD.
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Affiliation(s)
- Yanze Lin
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xugang Zhong
- Department of Orthopedics, Zhejiang Provincial People's Hospital, Qingdao University, Qingdao, China
| | - Dongning Lu
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Wenchao Yao
- Department of Orthopaedics, The First People's Hospital of Chun'an County, Hangzhou, Zhejiang, China
| | - Jinlei Zhou
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Ruiji Wu
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Fabo Feng
- Center for Plastic and Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
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20
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Liu X, Du Y, Zhao Z, Zou J, Zhang X, Zhang L. The multiple regulatory effects of white adipose tissue on bone homeostasis. J Cell Physiol 2023; 238:1193-1206. [PMID: 37120830 DOI: 10.1002/jcp.31025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 03/10/2023] [Accepted: 04/04/2023] [Indexed: 05/02/2023]
Abstract
White adipose tissue (WAT) is not only an energy storage reservoir that is critical in energy homeostasis but is also a highly metabolically active endocrine organ. WAT can secrete a variety of adipocytokines, including leptin (LEP), adiponectin (APN), resistin, visfatin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and osteopontin (OPN). It can also synthesize and secrete exosomes, which enhance intercellular communication and participate in various physiological processes in the body. It can also synthesize and secrete exosomes to enhance intercellular communication and participate in a variety of physiological processes in the body. The skeleton is an important organ for protecting internal organs. It forms the scaffolding of the body and gives the body its basic form. It drives muscle contraction to produce movement under the regulation of the nervous system. It is also an important hematopoietic organ; and it is regulated by the cytokines secreted by WAT. As research related to the release of adipocytokines from WAT to affect the skeleton continues to progress, an inextricable link between bone lipid regulation has been identified. In this paper, we review the literature to summarize the structure, function and metabolism of WAT, elaborate the specific molecular mechanisms by which WAT-secreted hormones, cytokines and exosomes regulate skeletal cells, provide a theoretical basis for the in-depth study of WAT cross-organ regulation of bone, and provide new ideas for finding new adipose-secreted targeting factors for the treatment of skeletal diseases.
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Affiliation(s)
- Xiaohua Liu
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Yuxiang Du
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Zhonghan Zhao
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Jun Zou
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Xiaojing Zhang
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lingli Zhang
- College of Athletic Performance, Shanghai University of Sport, Shanghai, China
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21
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Liu J, Zhao N, Su SH, Gao Y, Qi B. Anti-Arthritic Effect of Edaravone Against Complete Freund Adjuvant Induced Arthritis via Osteoclast Differentiation and HIF-1α-VEGF-ANG-1 Axis. Drug Des Devel Ther 2023; 17:519-534. [PMID: 36845667 PMCID: PMC9946814 DOI: 10.2147/dddt.s391606] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 12/15/2022] [Indexed: 02/19/2023] Open
Abstract
Background Bone dysfunction is a crucial problem that occurs during rheumatoid arthritis (RA) disease. Osteoclast plays a significant role in bone resorption and osteoclast differentiation and its enhancement of bone destruction. Edaravone remarkably exhibited free radical scavenging and anti-inflammatory effects. The objective of the current investigation is to comfort the inhibitory effect of Edaravone (ED) against complete Freund adjuvant (CFA) rat model via inhibition of angiogenesis and inflammation. Methods Subcutaneous injection of CFA (1%) was used to induce arthritis; the rats were divided into different groups and received the oral administration of ED. Paw edema, body weight, and arthritis score were regularly estimated. Biochemical parameters were estimated, respectively. We also estimate the level of hypoxia-inducible factor-1α (HIF-1α), angiopoietin 1 (ANG-1), and vascular endothelial growth factor (VEGF). We also checked into how ED affected the differentiation of osteoclasts utilising a co-culture system with monocytes and synovial fibroblasts in arthritis rats. Results ED treatment significantly (P<0.001) suppressed the arthritis score and paw edema and improved the body weight. ED treatment significantly (P<0.001) altered the antioxidant parameters and pro-inflammatory cytokines: inflammatory mediator nuclear kappa B factor (NF-κB), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2), respectively. Furthermore, ED treatment significantly (P<0.001) suppressed the level of ANG-1, HIF-1α, and VEGF, respectively. The results suggest that ED suppressed osteoclast differentiation and also decreased the level of cytokines and osteopontin (OPN), receptor activator for nuclear factor-κ B Ligand (RANKL) and macrophage colony stimulating factor (M-CSF) in the co-culture supernatant of monocytes and synovial fibroblasts. Conclusion Edaravone could mitigate CFA via inhibiting angiogenesis and inflammatory reactions, which may be linked with the HIF-1α-VEGF-ANG-1 axis and also enhance the bone destruction of murine arthritis via suppression of osteoclast differentiation and inflammatory reaction.
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Affiliation(s)
- Jichao Liu
- Department of Hand and Foot Micro Burn Plastic Surgery, 3201 Hospital, Hanzhong, People’s Republic of China
| | - Nan Zhao
- Department of Neurosurgery, The First Hospital of Kunming, Kunming, People’s Republic of China
| | - Shi-Han Su
- Department of Internal Medicine-Neurology, 920th Hospital of Joint Logistics Support Force, Kunming, People’s Republic of China
| | - Yun Gao
- Department of Neurosurgery, The First Hospital of Kunming, Kunming, People’s Republic of China
| | - Bo Qi
- Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force, Kunming, People’s Republic of China,Correspondence: Bo Qi, Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force, Kunming, 650000, People’s Republic of China, Email
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22
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The Influence of Adipokines on Radiographic Damage in Inflammatory Rheumatic Diseases. Biomedicines 2023; 11:biomedicines11020536. [PMID: 36831072 PMCID: PMC9953013 DOI: 10.3390/biomedicines11020536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/06/2023] [Accepted: 02/10/2023] [Indexed: 02/15/2023] Open
Abstract
Inflammatory rheumatic diseases (IRDs) are complex immune-mediated diseases that are characterized by chronic inflammation of the joints. Rheumatoid arthritis (RA) and spondyloarthritis (SpA), including axial SpA (ax SpA) and psoriatic arthritis (PsA), are the most common forms of IRD. Both RA and ax SpA are characterized by a chronic course with progressive structural modifications, namely, cartilage damage and bone erosions in RA and osteoproliferative changes with spinal ossifications in ax SpA. The adipose tissue is involved in the pathophysiology of IRDs via the release of several proteins, namely, adipokines. Several adipokines with pro-inflammatory effects have been identified, such as leptin, adiponectin, visfatin and resistin. In this review, we discuss the role that adipokines may play in the structural modifications of the peripheral joints and/or axial skeleton. In RA, the role of leptin in structural damage remains controversial, while adiponectin and its high-molecular-weight isoform are known to have an influence on the development of bone erosions and radiographic progression. Resistin also appears to be a potent detrimental adipokine for the joints in RA. In ax SpA, visfatin seems to be an attractive candidate for radiographic progression, while leptin and adiponectin have negative effects on radiographic progression.
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23
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Hayashi C, Fukuda T, Kawakami K, Toyoda M, Nakao Y, Watanabe Y, Shinjo T, Sano T, Iwashita M, Yotsumoto K, Shida M, Taketomi T, Sanui T, Uchiumi T, Kanematsu T, Nishimura F. miR-1260b inhibits periodontal bone loss by targeting ATF6β mediated regulation of ER stress. Front Cell Dev Biol 2022; 10:1061216. [PMID: 36531939 PMCID: PMC9748617 DOI: 10.3389/fcell.2022.1061216] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 11/15/2022] [Indexed: 01/26/2024] Open
Abstract
The expression profiles of exosomal microRNAs (miRNAs) are regulated by the microenvironment, and appropriate priming with mesenchymal stem cells (MSCs) is one of the strategies to enhance the paracrine potency of MSCs. Our previous work demonstrated that exosomes from tumor necrosis factor (TNF)-α-primed human gingiva-derived MSCs (GMSCs) could be a therapeutic tool against periodontitis, and that TNFα-inducible exosomal miR-1260b is essential for the inhibition of alveolar bone loss. However, the precise molecular mechanism underlying miR-1260b-mediated inhibition of osteoclastogenesis is not yet fully understood. Here, we found that the activating transcription factor (ATF)-6β, a novel miR-1260b-targeting gene, is critical for the regulation of osteoclastogenesis under endoplasmic reticulum (ER) stress. An experimental periodontal mouse model demonstrated that induction of ER stress was accompanied by enhanced ATF6β expression, and local administration of miR-1260b and ATF6β siRNA using polyethylenimine nanoparticles (PEI-NPs) significantly suppressed the periodontal bone resorption. In periodontal ligament (PDL) cells, the ER stress inducer, tunicamycin, enhanced the expression of the receptor activator of NF-κB ligand (RANKL), while miR-1260b-mediated downregulation of ATF6β caused RANKL inhibition. Furthermore, the secretome from miR-1260b/ATF6β-axis-activated PDL cells inhibited osteoclastogenesis in human CD14+ peripheral blood-derived monocytes. These results indicate that the miR-1260b/ATF6β axis mediates the regulation of ER stress, which may be used as a novel therapeutic strategy to treat periodontal disease.
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Affiliation(s)
- Chikako Hayashi
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Takao Fukuda
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Kentaro Kawakami
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Masaaki Toyoda
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Yuki Nakao
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Yukari Watanabe
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Takanori Shinjo
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Tomomi Sano
- Department of Cell Biology, Aging Science, and Pharmacology, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Misaki Iwashita
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Karen Yotsumoto
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Miyu Shida
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Takaharu Taketomi
- Dental and Oral Medical Center, Kurume University School of Medicine, Fukuoka, Japan
| | - Terukazu Sanui
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Takeshi Uchiumi
- Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takashi Kanematsu
- Department of Cell Biology, Aging Science, and Pharmacology, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Fusanori Nishimura
- Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
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González-Rodríguez M, Ruiz-Fernández C, Cordero-Barreal A, Ait Eldjoudi D, Pino J, Farrag Y, Gualillo O. Adipokines as targets in musculoskeletal immune and inflammatory diseases. Drug Discov Today 2022; 27:103352. [PMID: 36099964 DOI: 10.1016/j.drudis.2022.103352] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 07/28/2022] [Accepted: 09/06/2022] [Indexed: 11/21/2022]
Abstract
Adipokines are the principal mediators in adipose signaling. Nevertheless, besides their role in energy storage, these molecules can be produced by other cells, such as immune cells or chondrocytes. Given their pleiotropic effects, research over the past few years has also focused on musculoskeletal diseases, showing that these adipokines might have relevant roles in worsening the disease or improving the treatment response. In this review, we summarize recent advances in our understanding of adipokines and their role in the most prevalent musculoskeletal immune and inflammatory disorders.
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Affiliation(s)
- María González-Rodríguez
- SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain; International PhD School of the University of Santiago de Compostela (EDIUS), Doctoral Programme in Drug Research and Development, Santiago de Compostela, Spain
| | - Clara Ruiz-Fernández
- SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain; International PhD School of the University of Santiago de Compostela (EDIUS), Doctoral Programme in Medicine Clinical Research, Santiago de Compostela, Spain
| | - Alfonso Cordero-Barreal
- SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain; International PhD School of the University of Santiago de Compostela (EDIUS), Doctoral Programme in Molecular Medicine, Santiago de Compostela, Spain
| | - Djedjiga Ait Eldjoudi
- SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain
| | - Jesus Pino
- SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain; Departamento de Cirurgía y Especialidades Médico-Cirúrgicas Área de Traumatología e Ortopedia, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
| | - Yousof Farrag
- SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain.
| | - Oreste Gualillo
- SERGAS (Servizo Galego de Saude) and NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS (Instituto de Investigación Sanitaria de Santiago), Santiago University Clinical Hospital, Santiago de Compostela, Spain.
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25
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Normand E, Franco A, Alos N, Parent S, Moreau A, Marcil V. Circulatory Adipokines and Incretins in Adolescent Idiopathic Scoliosis: A Pilot Study. CHILDREN (BASEL, SWITZERLAND) 2022; 9:1619. [PMID: 36360347 PMCID: PMC9688531 DOI: 10.3390/children9111619] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 10/20/2022] [Accepted: 10/21/2022] [Indexed: 08/26/2023]
Abstract
Adolescent idiopathic scoliosis (AIS) is a three-dimensional malformation of the spine of unknown cause that develops between 10 and 18 years old and affects 2-3% of adolescents, mostly girls. It has been reported that girls with AIS have a taller stature, lower body mass index (BMI), and bone mineral density (BMD) than their peers, but the causes remain unexplained. Energy metabolism discrepancies, including alterations in adipokine and incretin circulatory levels, could influence these parameters and contribute to disease pathophysiology. This pilot study aims to compare the anthropometry, BMD, and metabolic profile of 19 AIS girls to 19 age-matched healthy controls. Collected data include participants' fasting metabolic profile, anthropometry (measurements and DXA scan), nutritional intake, and physical activity level. AIS girls (14.8 ± 1.7 years, Cobb angle 27 ± 10°), compared to controls (14.8 ± 2.1 years), were leaner (BMI-for-age z-score ± SD: -0.59 ± 0.81 vs. 0.09 ± 1.11, p = 0.016; fat percentage: 24.4 ± 5.9 vs. 29.2 ± 7.2%, p = 0.036), had lower BMD (total body without head z-score ± SD: -0.6 ± 0.83 vs. 0.23 ± 0.98, p = 0.038; femoral neck z-score: -0.54 ± 1.20 vs. 0.59 ± 1.59, p = 0.043), but their height was similar. AIS girls had higher adiponectin levels [56 (9-287) vs. 32 (7-74) μg/mL, p = 0.005] and lower leptin/adiponectin ratio [0.042 (0.005-0.320) vs. 0.258 (0.024-1.053), p = 0.005]. AIS participants with a Cobb angle superior to 25° had higher resistin levels compared to controls [98.2 (12.8-287.2) vs. 32.1 (6.6-73.8), p = 0.0013]. This pilot study suggests that adipokines are implicated in AIS development and/or progression, but more work is needed to confirm their role in the disease.
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Affiliation(s)
- Emilie Normand
- Research Center of the CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada
- Department of Nutrition, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada
| | - Anita Franco
- Research Center of the CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada
- Viscogliosi Laboratory in Molecular Genetics and Musculoskeletal Diseases, Research Center of the CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada
| | - Nathalie Alos
- Endocrine Service, Department of Pediatrics, CHU Sainte-Justine, Montreal, QC H3T 1J4, Canada
| | - Stefan Parent
- Department of Surgery, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada
| | - Alain Moreau
- Viscogliosi Laboratory in Molecular Genetics and Musculoskeletal Diseases, Research Center of the CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada
- Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada
- Department of Stomatology, Faculty of Dentistry, Université de Montréal, Montreal, QC H3A 1J4, Canada
| | - Valérie Marcil
- Research Center of the CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada
- Department of Nutrition, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada
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Obesity and Bone Health: A Complex Relationship. Int J Mol Sci 2022; 23:ijms23158303. [PMID: 35955431 PMCID: PMC9368241 DOI: 10.3390/ijms23158303] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/21/2022] [Accepted: 07/25/2022] [Indexed: 02/07/2023] Open
Abstract
Recent scientific evidence has shown an increased risk of fractures in patients with obesity, especially in those with a higher visceral adipose tissue content. This contradicts the old paradigm that obese patients were more protected than those with normal weight. Specifically, in older subjects in whom there is a redistribution of fat from subcutaneous adipose tissue to visceral adipose tissue and an infiltration of other tissues such as muscle with the consequent sarcopenia, obesity can accentuate the changes characteristic of this age group that predisposes to a greater risk of falls and fractures. Other factors that determine a greater risk in older subjects with obesity are chronic proinflammatory status, altered adipokine secretion, vitamin D deficiency, insulin resistance and reduced mobility. On the other hand, diagnostic tests may be influenced by obesity and its comorbidities as well as by body composition, and risk scales may underestimate the risk of fractures in these patients. Weight loss with physical activity programs and cessation of high-fat diets may reduce the risk. Finally, more research is needed on the efficacy of anti-osteoporotic treatments in obese patients.
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27
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The Influence of Nesfatin-1 on Bone Metabolism Markers Concentration, Densitometric, Tomographic and Mechanical Parameters of Skeletal System of Rats in the Conditions of Established Osteopenia. Animals (Basel) 2022; 12:ani12050654. [PMID: 35268222 PMCID: PMC8909152 DOI: 10.3390/ani12050654] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/28/2022] [Accepted: 03/03/2022] [Indexed: 12/02/2022] Open
Abstract
Simple Summary Nesfatin-1 is an adipokine with little known effect on the skeletal system. In this study, we examined the effect of 8-wk administration of nesfatin-1 on densitometric, tomographic, and mechanical parameters of bones, as well as the concentration of bone metabolism markers in rats with experimentally induced established osteopenia. Abstract Our study aimed to evaluate the impact of nesfatin-1 administration on bone metabolism and properties in established osteopenia in ovariectomized female rats. In total, 21 female Wistar rats were assigned to two groups: sham-operated (SHAM, n = 7) and ovariectomized (OVA, n = 14). After 12 weeks of osteopenia induction in the OVA females, the animals were given i.p. physiological saline (OVA, n = 7) or 2 µg/kg body weight of nesfatin-1(NES, n = 7) for the next 8 weeks. The SHAM animals received physiological saline at the same time. Final body weight, total bone mineral density and content of the skeleton were estimated. Then, isolated femora and tibias were subjected to densitometric, tomographic, and mechanical tests. Bone metabolism markers, i.e., osteocalcin, bone specific alkaline phosphatase (bALP), and crosslinked N-terminal telopeptide of type I collagen (NTx) were determined in serum using an ELISA kit. Ovariectomy led to negative changes in bone metabolism associated with increased resorption, thus diminishing the densitometric, tomographic, and mechanical parameters. In turn, the administration of nesfatin-1 led to an increase in the value of the majority of the tested parameters of bones. The lowest bALP concentration and the highest NTx concentration were found in the OVA females. The bALP concentration was significantly higher after nesfatin-1 administration in comparison to the OVA rats. In conclusion, the results indicate that nesfatin-1 treatment limits bone loss, preserves bone architecture, and increases bone strength in condition of established osteopenia.
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28
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Mendonça F, Soares R, Carvalho D, Freitas P. The Impact of Bariatric Surgery on Bone Health: State of the Art and New Recognized Links. Horm Metab Res 2022; 54:131-144. [PMID: 35276738 DOI: 10.1055/a-1767-5581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Bariatric surgery (BS) is the most effective therapy for severe obesity, which improves several comorbidities (such as diabetes, hypertension, dyslipidemia, among others) and results in marked weight loss. Despite these consensual beneficial effects, sleeve gastrectomy and Roux-en-Y gastric bypass (the two main bariatric techniques) have also been associated with changes in bone metabolism and progressive bone loss. The objective of this literature review is to examine the impact of bariatric surgery on bone and its main metabolic links, and to analyze the latest findings regarding the risk of fracture among patients submitted to bariatric surgery.
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Affiliation(s)
- Fernando Mendonça
- Serviço de Endocrinologia, Diabetes e Metabolismo, Centro Hospitalar e Universitário de S. João, Porto, Portugal
- Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Raquel Soares
- Faculdade de Medicina da Universidade do Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Davide Carvalho
- Serviço de Endocrinologia, Diabetes e Metabolismo, Centro Hospitalar e Universitário de S. João, Porto, Portugal
- Faculdade de Medicina da Universidade do Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
| | - Paula Freitas
- Serviço de Endocrinologia, Diabetes e Metabolismo, Centro Hospitalar e Universitário de S. João, Porto, Portugal
- Faculdade de Medicina da Universidade do Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
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29
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Tang C, Liang D, Qiu Y, Zhu J, Tang G. Omentin‑1 induces osteoblast viability and differentiation via the TGF‑β/Smad signaling pathway in osteoporosis. Mol Med Rep 2022; 25:132. [PMID: 35179221 PMCID: PMC8867465 DOI: 10.3892/mmr.2022.12648] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 07/13/2021] [Indexed: 11/25/2022] Open
Abstract
Osteoporosis is a bone-related disease that results from impaired bone formation and excessive bone resorption. The potential value of adipokines has been investigated previously, due to their influence on osteogenesis. However, the osteogenic effects induced by omentin-1 remain unclear. The aim of the present study was to determine the regulatory effects of omentin-1 on osteoblast viability and differentiation, as well as to explore the underlying molecular mechanism. The present study investigated the effects of omentin-1 on the viability and differentiation of mouse pre-osteoblast cells (MC3T3-E1) using quantitative and qualitative measures. A Cell Counting Kit-8 assay was used to assess the viability of MC3T3-E1 cells following treatment with different doses of omentin-1. Omentin-1 and bone morphogenetic protein (BMP) inhibitor were added to osteogenic induction mediums in different ways to assess their effect. The alkaline phosphatase (ALP) activity and Alizarin Red S (ARS) staining of MC3T3-E1 cells treated with omentin-1 and/or BMP inhibitor were used to examine the effects of omentin-1 on differentiation and mineralization. Western blotting was used to further explore its potential mechanism, and to study the role of omentin-1 on the viability and differentiation of osteoblasts. The results showed that omentin-1 altered the viability of MC3T3-E1 cells in a dose-dependent manner. Omentin-1 treatment significantly increased the expression of members of the TGF-β/Smad signaling pathway. In the omentin-1 group, the ALP activity of the MC3T3-E1 cells was increased, and the ARS staining area was also increased. The mRNA and protein expression levels of BMP2, Runt-related transcription factor 2, collagen1, osteopontin, osteocalcin and osterix in the omentin-1 group were also significantly upregulated. All these effects were reversed following treatment with SIS3 HCl. These results demonstrated that omentin-1 can significantly promote osteoblast viability and differentiation via the TGF-β/Smad signaling pathway, thereby promoting bone formation and preventing osteoporosis.
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Affiliation(s)
- Cuisong Tang
- Department of Radiology, Clinical Medical College of Shanghai Tenth People's Hospital of Nanjing Medical University, Shanghai 200072, P.R. China
| | - Dengpan Liang
- Department of Cardiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China
| | - Yuyou Qiu
- Department of Radiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Jingqi Zhu
- Department of Radiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Guangyu Tang
- Department of Radiology, Clinical Medical College of Shanghai Tenth People's Hospital of Nanjing Medical University, Shanghai 200072, P.R. China
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Body Composition as a Modulator of Bone Health Changes in Patients with Inflammatory Bowel Disease. Life (Basel) 2022; 12:life12020272. [PMID: 35207559 PMCID: PMC8875340 DOI: 10.3390/life12020272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/09/2022] [Accepted: 02/10/2022] [Indexed: 12/05/2022] Open
Abstract
Background: Bone impairment of multifactorial etiology is a common feature in inflammatory bowel disease (IBD). Body composition parameters, which might be selectively modified in these patients, are important determinants of bone strength. Our aim was to investigate the relationship between components of body composition and bone parameters in IBD patients. Methods: This is a cross-sectional, retrospective study including 80 IBD patients (43 women, 37 men). Lumbar spine (LS), femoral neck (FN) and whole body DXA scans were performed to analyze regional bone mineral density (BMD), as well as body composition, including appendicular skeletal muscle mass index (ASMI), total and visceral fat mass (VAT). Trabecular bone score (TBS) was assessed using iNsight Software. Results: Twenty (25%) IBD patients had inadequate LS-BMD z scores (<=−2DS). Lean mass (LM) was a significant determinant of LS-BMD, after adjusting for age, gender, BMI and fat mass (p < 0.01), while fat mass% remained associated with FN-BMD (p < 0.01). TBS correlated positively with BMI (r = 0.24, p < 0.05), LS-BMD (r = 0.56, p < 0.001), ASMI (r = 0.34, p < 0.001) and negatively with VAT/total fat% (r = −0.27, p < 0.05). Multivariate analysis showed that ASMI, LS-BMD (positively) and VAT/total fat% (negatively) were independently associated with TBS. Conclusions: In IBD patients, skeletal muscle mass and fat percentage and distribution are important factors associated with bone health.
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He B, Zhao J, Zhang M, Yin L, Quan Z, Ou Y, Huang W. Causal roles of circulating adiponectin in osteoporosis and cancers. Bone 2022; 155:116266. [PMID: 34844025 DOI: 10.1016/j.bone.2021.116266] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 11/07/2021] [Accepted: 11/22/2021] [Indexed: 01/04/2023]
Abstract
Circulating adiponectin has some association with the risk of osteoporosis and cancers, but their causal relationships remains elusive. Mendelian randomization (MR) study was used to explore the causal roles of circulating adiponectin in osteoporosis and cancers by using genome-wide association studies (GWASs) associated with circulating adiponectin, osteoporosis and cancers. Fifteen single nucleotide polymorphisms (SNPs) were used as instrumental variables for circulating adiponectin. Genetic predisposition to high circulating adiponectin was strongly associated with low femoral neck bone mineral density (FN-BMD, beta-estimate: -0.015, 95% CI: -0.023 to -0.006, SE: 0.004, P-value = 0.001), low forearm BMD (FA-BMD, beta-estimate: -0.027, 95% CI: -0.050 to -0.004, SE: 0.012, P-value = 0.023) and increased risk of breast cancer (beta-estimate: 0.011, 95% CI: 0.001 to 0.022, SE: 0.005, P-value = 0.031). There was limited evidence of the associations between circulating adiponectin and other outcomes (i.e. lumbar spine BMD [LS-BMD], colorectal cancer, liver cancer, lung cancer, bone cancer and prostate cancer). This study provides robust evidence that high circulating adiponectin is causally associated with low FN-BMD, low FA-BMD and increased risk of breast cancer, which may provide new insight to prevent and treat osteoporosis and breast cancer.
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Affiliation(s)
- Bin He
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jinqiu Zhao
- Department of Infectious diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Muzi Zhang
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Lifeng Yin
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Zhengxue Quan
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yunsheng Ou
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
| | - Wei Huang
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
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Mele C, Caputo M, Ferrero A, Daffara T, Cavigiolo B, Spadaccini D, Nardone A, Prodam F, Aimaretti G, Marzullo P. Bone Response to Weight Loss Following Bariatric Surgery. Front Endocrinol (Lausanne) 2022; 13:921353. [PMID: 35873004 PMCID: PMC9301317 DOI: 10.3389/fendo.2022.921353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 05/23/2022] [Indexed: 11/28/2022] Open
Abstract
Obesity is a global health challenge that warrants effective treatments to avoid its multiple comorbidities. Bariatric surgery, a cornerstone treatment to control bodyweight excess and relieve the health-related burdens of obesity, can promote accelerated bone loss and affect skeletal strength, particularly after malabsorptive and mixed surgical procedures, and probably after restrictive surgeries. The increase in bone resorption markers occurs early and persist for up to 12 months or longer after bariatric surgery, while bone formation markers increase but to a lesser extent, suggesting a potential uncoupling process between resorption and formation. The skeletal response to bariatric surgery, as investigated by dual-energy X-ray absorptiometry (DXA), has shown significant loss in bone mineral density (BMD) at the hip with less consistent results for the lumbar spine. Supporting DXA studies, analyses by high-resolution peripheral quantitative computed tomography (HR-pQCT) showed lower cortical density and thickness, higher cortical porosity, and lower trabecular density and number for up to 5 years after bariatric surgery. These alterations translate into an increased risk of fall injury, which contributes to increase the fracture risk in patients who have been subjected to bariatric surgery procedures. As bone deterioration continues for years following bariatric surgery, the fracture risk does not seem to be dependent on acute weight loss but, rather, is a chronic condition with an increasing impact over time. Among the post-bariatric surgery mechanisms that have been claimed to act globally on bone health, there is evidence that micro- and macro-nutrient malabsorptive factors, mechanical unloading and changes in molecules partaking in the crosstalk between adipose tissue, bone and muscle may play a determining role. Given these circumstances, it is conceivable that bone health should be adequately investigated in candidates to bariatric surgery through bone-specific work-up and dedicated postsurgical follow-up. Specific protocols of nutrients supplementation, motor activity, structured rehabilitative programs and, when needed, targeted therapeutic strategies should be deemed as an integral part of post-bariatric surgery clinical support.
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Affiliation(s)
- Chiara Mele
- Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
- *Correspondence: Chiara Mele,
| | - Marina Caputo
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Division of Endocrinology, University Hospital “Maggiore della Carità”, Novara, Italy
| | - Alice Ferrero
- Division of Endocrinology, University Hospital “Maggiore della Carità”, Novara, Italy
| | - Tommaso Daffara
- Division of Endocrinology, University Hospital “Maggiore della Carità”, Novara, Italy
| | - Beatrice Cavigiolo
- Division of Endocrinology, University Hospital “Maggiore della Carità”, Novara, Italy
| | - Daniele Spadaccini
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | - Antonio Nardone
- Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
- Istituti Clinici Scientifici Maugeri IRCCS, Neurorehabilitation and Spinal Unit of Pavia Institute, Pavia, and Neurorehabilitation of Montescano Institute, Montescano, PV, Italy
| | - Flavia Prodam
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Division of Endocrinology, University Hospital “Maggiore della Carità”, Novara, Italy
| | - Gianluca Aimaretti
- Division of Endocrinology, University Hospital “Maggiore della Carità”, Novara, Italy
- Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
| | - Paolo Marzullo
- Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
- Istituto Auxologico Italiano, IRCCS, Laboratory of Metabolic Research, S. Giuseppe Hospital, Piancavallo, Italy
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Pal S, Singh M, Porwal K, Rajak S, Das N, Rajput S, Trivedi AK, Maurya R, Sinha RA, Siddiqi MI, Sanyal S, Chattopadhyay N. Adiponectin receptors by increasing mitochondrial biogenesis and respiration promote osteoblast differentiation: Discovery of isovitexin as a new class of small molecule adiponectin receptor modulator with potential osteoanabolic function. Eur J Pharmacol 2021; 913:174634. [PMID: 34785210 DOI: 10.1016/j.ejphar.2021.174634] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 10/29/2021] [Accepted: 11/11/2021] [Indexed: 10/19/2022]
Abstract
Previously, we established adiponectin receptors (AdipoRs) as osteoanabolic target. To discover small molecule agonists of AdipoRs, we studied apigenin and apigenin-6C-glucopyranose (isovitexin) that induced osteoblast differentiation. In-silico, in vitro and omics-based studies were performed. Molecular docking using the crystal structures of AdipoRs showed different interaction profiles of isovitexin and apigenin. In osteoblasts, isovitexin but not apigenin rapidly phosphorylated AMP-activated protein kinase (pAMPK) which is downstream of AdipoRs and a master regulator of cellular energy metabolism, and upregulated expression of AdipoRs. Blocking AMPK abolished the osteogenic effect of isovitexin and its effect on AdipoR expression. Isovitexin upregulated the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), the mitochondrial biogenesis factor in osteoblasts, and the effect was blocked by AMPK inhibition. Upregulation of PGC-1α by isovitexin was accompanied by increased mitochondrial membrane proteins and mitochondrial DNA (mtDNA). Isovitexin via AdipoRs and PGC-1α induced oxidative phosphorylation (OxPhos) and ATP synthesis that resulted in osteoblast differentiation. Isovitexin had no agonistic/antagonistic activity and stimulatory/inhibitory effect in screening platforms for G protein-coupled receptors and kinases, respectively. In vivo, isovitexin upregulated AdipoRs and osteogenic genes, and increased mtDNA in rat calvarium. We conclude that isovitexin selectively via AdipoRs induced osteoblast differentiation that was fuelled by mitochondrial respiration.
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Affiliation(s)
- Subhashis Pal
- Division of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India
| | - Maninder Singh
- Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India
| | - Konica Porwal
- Division of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India
| | - Sangam Rajak
- Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Nabanita Das
- Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India
| | - Swati Rajput
- Division of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India
| | - Arun K Trivedi
- Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India
| | - Rakesh Maurya
- Division of Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India
| | - Rohit A Sinha
- Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Mohammad I Siddiqi
- Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India
| | - Sabyasachi Sanyal
- Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India
| | - Naibedya Chattopadhyay
- Division of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India.
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Zhou S, Wang X, Shi J, Han Q, He L, Tang W, Zhang A. Serum fatty acid binding protein 4 levels are associated with abdominal aortic calcification in peritoneal dialysis patients. Ren Fail 2021; 43:1539-1548. [PMID: 34789046 PMCID: PMC8604498 DOI: 10.1080/0886022x.2021.2003205] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background Fatty acid binding protein 4 (FABP4) is an adipokine that was mainly derived from adipocytes and macrophages. Vascular calcification (VC) is highly prevalent in peritoneal dialysis (PD) patients and could predict their cardiovascular mortality. The pathogenesis of VC is complex, and adipokines may play an important role in it. This study aimed to examine the relationship between serum FABP4 and VC in PD patients. Methods Serum FABP4 was measured by enzyme-linked immunosorbent assay. According to the median value of serum FABP4, the participants were divided into the low FABP4 group and the high FABP4 group. Lateral plain X-ray films of abdomen were used to evaluate the abdominal aortic calcification (AAC) score. The participants were divided into the high AAC score group (AAC score ≥4, indicating moderate or heavy VC) and the low AAC score group (AAC score <4, indicating no or mild VC). Results 116 PD patients were involved in the study. The AAC score and the proportion of patients with an AAC score ≥4 of the high FABP4 group were significantly higher than those of the low FABP4 group. Serum FABP4 of the high AAC score group was significantly higher than that of the low AAC score group [164.5 (138.4, 362.8) ng/mL versus 144.7 (123.8, 170.1) ng/mL, p = 0.002]. Serum FABP4 was positively associated with the AAC score according to the multivariate linear regression analysis. In the multivariate logistic regression analysis, serum FABP4 was the independent influencer of an AAC score ≥4. Conclusions Serum FABP4 is positively associated with the AAC score and is an independent marker of AAC in PD patients.
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Affiliation(s)
- Sijia Zhou
- Department of Nephrology, Peking University Third Hospital, Beijing, China
| | - Xiaoxiao Wang
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
| | - Junbao Shi
- Department of Nephrology, Peking University Third Hospital, Beijing, China
| | - Qingfeng Han
- Department of Nephrology, Peking University Third Hospital, Beijing, China
| | - Lian He
- Department of Nephrology, Peking University Third Hospital, Beijing, China
| | - Wen Tang
- Department of Nephrology, Peking University Third Hospital, Beijing, China
| | - Aihua Zhang
- Department of Nephrology, Xuanwu Hospital Capital Medical University, Beijing, China
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Gong Y, Wang Y, Zhang Y, Wang L, Wan L, Zu Y, Li C, Wang X, Cui ZK. Paracrine Effects of Recombinant Human Adiponectin Promote Bone Regeneration. Front Cell Dev Biol 2021; 9:762335. [PMID: 34790669 PMCID: PMC8591230 DOI: 10.3389/fcell.2021.762335] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 09/27/2021] [Indexed: 01/15/2023] Open
Abstract
Bone regeneration is a delicate physiological process. Non-union and delayed fracture healing remains a great challenge in clinical practice nowadays. Bone and fat hold a close relationship to remain balanced through hormones and cytokines. Adiponectin is a well-known protein to maintain the hemostasis, which may be an interesting target for fracture healing. Herein, we provided a facile and efficient method to obtain high-purity and high-yield recombinant human adiponectin (ADPN). The biocompatibility and the pharmaceutical behaviors were evaluated in Sprague–Dawley rats. The paracrine effects of adiponectin on bone fracture healing were investigated with a rat tibia fracture model via intrabone injection. Significantly accelerated bone healing was observed in the medulla injection group, indicating the paracrine effects of adiponectin could be potentially utilized for clinical treatments. The underlying mechanism was primarily assessed, and the expression of osteogenic markers, including bone morphogenic protein 2, alkaline phosphatase, and osteocalcin, along with adiponectin receptor 1 (AdipoR1), was markedly increased at the fracture site. The increased bone healing of ADPN treatment may result from both enhanced osteogenic proliferation as well as differentiation. Cell experiments confirmed that the expression of osteogenesis markers increased significantly in ADPN treatment groups, while it decreased when the expression of AdipoR1 was knocked down by siRNA. Our study provided a feasible and efficacious way for bone fracture treatment with local administration of ADPN, which could be rapidly translated into the clinics.
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Affiliation(s)
- Yanping Gong
- Department of Endocrinology, The Second Medical Center, National Clinical Research Center for Geriatric Disease, The Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yang Wang
- Department of Endocrinology, The Second Medical Center, National Clinical Research Center for Geriatric Disease, The Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yiqing Zhang
- Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China
| | - Liangchen Wang
- Department of Endocrinology, The Second Medical Center, National Clinical Research Center for Geriatric Disease, The Chinese People's Liberation Army General Hospital, Beijing, China
| | - Lijuan Wan
- Department of Endocrinology, The Second Medical Center, National Clinical Research Center for Geriatric Disease, The Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yuan Zu
- Department of Endocrinology, The Second Medical Center, National Clinical Research Center for Geriatric Disease, The Chinese People's Liberation Army General Hospital, Beijing, China
| | - Chunlin Li
- Department of Endocrinology, The Second Medical Center, National Clinical Research Center for Geriatric Disease, The Chinese People's Liberation Army General Hospital, Beijing, China
| | - Xin Wang
- Institute of Orthopedics, The First Medical Center, The People's Liberation Army General Hospital, Beijing, China
| | - Zhong-Kai Cui
- Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.,Bioland Laboratory, Guangzhou, China
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Freire EBL, d’Alva CB, Madeira MP, Lima GEDCP, Montenegro APDR, Fernandes VO, Montenegro Junior RM, Brazilian Group for the Study of Inherited and Acquired Lipodystrophies (BRAZLIPO). Bone Mineral Density in Congenital Generalized Lipodystrophy: The Role of Bone Marrow Tissue, Adipokines, and Insulin Resistance. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:9724. [PMID: 34574647 PMCID: PMC8465110 DOI: 10.3390/ijerph18189724] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/05/2021] [Accepted: 07/16/2021] [Indexed: 12/31/2022]
Abstract
Congenital Generalized Lipodystrophy (CGL) is a rare syndrome characterized by the almost total absence of subcutaneous adipose tissue due to the inability of storing lipid in adipocytes. Patients present generalized lack of subcutaneous fat and normal to low weight. They evolve with severe metabolic disorders, non-alcoholic fatty liver disease, early cardiac abnormalities, and infectious complications. Although low body weight is a known risk factor for osteoporosis, it has been reported that type 1 and 2 CGL have a tendency of high bone mineral density (BMD). In this review, we discuss the role of bone marrow tissue, adipokines, and insulin resistance in the setting of the normal to high BMD of CGL patients. Data bases from Pubmed and LILACS were searched, and 113 articles published until 10 April 2021 were obtained. Of these, 76 were excluded for not covering the review topic. A manual search for additional literature was performed using the bibliographies of the studies located. The elucidation of the mechanisms responsible for the increase in BMD in this unique model of insulin resistance may contribute to the understanding of the interrelationships between bone, muscle, and adipose tissue in a pathophysiological and therapeutic perspective.
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Affiliation(s)
| | | | | | | | | | | | - Renan Magalhães Montenegro Junior
- Clinical Research Unit, Walter Cantídio University Hospital, Federal University of Ceará, Fortaleza 60416200, CE, Brazil; (E.B.L.F.); (C.B.d.); (M.P.M.); (G.E.d.C.P.L.); (A.P.D.R.M.); (V.O.F.)
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Huang Z, Chu L, Liang J, Tan X, Wang Y, Wen J, Chen J, Wu Y, Liu S, Liao J, Hou R, Ding Z, Zhang Z, Liang H, Song S, Yang C, Zhang J, Guo T, Chen X, Zhang B. H19 Promotes HCC Bone Metastasis Through Reducing Osteoprotegerin Expression in a Protein Phosphatase 1 Catalytic Subunit Alpha/p38 Mitogen-Activated Protein Kinase-Dependent Manner and Sponging microRNA 200b-3p. Hepatology 2021; 74:214-232. [PMID: 33615520 DOI: 10.1002/hep.31673] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 11/06/2020] [Accepted: 11/13/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS Bone is the second most frequent site of metastasis for HCC, which leads to an extremely poor prognosis. HCC bone metastasis is typically osteolytic, involving the activation of osteoclasts. Long noncoding RNA H19 plays an important role in the pathogenesis of human cancers. Nonetheless, the mechanism underlying the participation of H19 in HCC bone metastasis remains unclear. APPROACH AND RESULTS The current study established a mouse HCC bone metastasis model by using serial intracardiac injection and cell isolation to obtain cells with distinct bone metastasis ability. H19 was highly expressed in these cells and in clinical HCC bone metastasis specimens. Both osteoclastogenesis in vitro and HCC bone metastasis in vivo were promoted by H19 overexpression, whereas these processes were suppressed by H19 knockdown. H19 overexpression attenuated p38 phosphorylation and further down-regulated the expression of osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor. However, up-regulated OPG expression as well as suppressed osteoclastogenesis caused by H19 knockdown were recovered by p38 interference, indicating that p38 mitogen-activated protein kinase (MAPK)-OPG contributed to H19-promoted HCC bone metastasis. Furthermore, we demonstrated that H19 inhibited the expression of OPG by binding with protein phosphatase 1 catalytic subunit alpha (PPP1CA), which dephosphorylates p38. SB-203580-mediated inactivation of p38MAPK reversed the down-regulation of HCC bone metastasis caused by H19 knockdown in vivo. Additionally, H19 enhanced cell migration and invasion by up-regulating zinc finger E-box binding homeobox 1 through the sequestration of microRNA (miR) 200b-3p. CONCLUSIONS H19 plays a critical role in HCC bone metastasis by reducing OPG expression, which is mediated by the PPP1CA-induced inactivation of the p38MAPK pathway; and H19 also functions as a sponge for miR-200b-3p.
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Affiliation(s)
- Zhao Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Liang Chu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Junnan Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Xiaolong Tan
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Yu Wang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Jingyuan Wen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Jin Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Yu Wu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Sha Liu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Jingyu Liao
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Rui Hou
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zeyang Ding
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Zhanguo Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Huifang Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Shasha Song
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
| | - Caihong Yang
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jinming Zhang
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Guo
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
- Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China
- Key Laboratory of Organ Transplantation, National Health Commission, Wuhan, China
- Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China
- Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China
- Key Laboratory of Organ Transplantation, National Health Commission, Wuhan, China
- Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
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Liu H, Liu S, Ji H, Zhao Q, Liu Y, Hu P, Luo E. An adiponectin receptor agonist promote osteogenesis via regulating bone-fat balance. Cell Prolif 2021; 54:e13035. [PMID: 33939201 PMCID: PMC8168410 DOI: 10.1111/cpr.13035] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/09/2021] [Accepted: 03/15/2021] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES Adiponectin signalling has been considered to be a promising target to treat diabetes-related osteoporosis. However, contradictory results regarding bone formation were observed due to the various isoforms of adiponectin. Therefore, it would be necessary to investigate the effect of adiponectin receptor signals in regulating bone-fat balance. MATERIALS AND METHODS We primarily applied a newly found specific activator for adiponectin receptor, AdipoRon, to treat bone metabolism-related cells to investigate the role of Adiponectin receptor signals on bone-fat balance. We then established femur defect mouse model and treated them with AdipoRon to see whether adiponectin receptor activation could promote bone regeneration. RESULTS We found that AdipoRon could slightly inhibit the proliferation of pre-osteoblast and pre-osteoclast, but AdipoRon showed no effect on the viability of mesenchymal stromal cells. AdipoRon could remarkably promote cell migration of mesenchymal stromal cells. Additionally, AdipoRon promoted osteogenesis in both pre-osteoblasts and mesenchymal cells. Besides, AdipoRon significantly inhibited osteoclastogenesis via its direct impact on pre-osteoclast and its indirect inhibition of RANKL in osteoblast. Moreover, mesenchymal stromal stems cells showed obviously decreased adipogenesis when treated with AdipoRon. Consistently, AdipoRon-treated mice showed faster bone regeneration and repressed adipogenesis. CONCLUSIONS Our study demonstrated a pro-osteogenic, anti-adipogenic and anti-osteoclastogenic effect of adiponectin receptor activation in young mice, which suggested adiponectin receptor signalling was involved in bone regeneration and bone-fat balance regulation.
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Affiliation(s)
- Hanghang Liu
- State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & Department of Oral Maxillofacial SurgeryWest China Hospital of StomatologySichuan UniversityChengduSichuanP. R. China
- Maine Medical Center Research InstituteMaine Medical CenterScarboroughMEUSA
| | - Shibo Liu
- State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & Department of Oral Maxillofacial SurgeryWest China Hospital of StomatologySichuan UniversityChengduSichuanP. R. China
| | - Huanzhong Ji
- State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & Department of Oral Maxillofacial SurgeryWest China Hospital of StomatologySichuan UniversityChengduSichuanP. R. China
| | - Qiucheng Zhao
- State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & Department of Oral Maxillofacial SurgeryWest China Hospital of StomatologySichuan UniversityChengduSichuanP. R. China
| | - Yao Liu
- State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & Department of Oral Maxillofacial SurgeryWest China Hospital of StomatologySichuan UniversityChengduSichuanP. R. China
| | - Pei Hu
- State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & Department of Oral Maxillofacial SurgeryWest China Hospital of StomatologySichuan UniversityChengduSichuanP. R. China
| | - En Luo
- State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & Department of Oral Maxillofacial SurgeryWest China Hospital of StomatologySichuan UniversityChengduSichuanP. R. China
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Amouzegar A, Asgari S, Azizi F, Momenan AA, Bozorgmanesh M, Hadaegh F. The Role of Metabolic Syndrome and its Components in Incident Fracture: A 15-Year Follow-Up Among the Iranian Population. J Clin Endocrinol Metab 2021; 106:e1968-e1983. [PMID: 33522577 DOI: 10.1210/clinem/dgab023] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Indexed: 12/15/2022]
Abstract
CONTEXT The relationship between metabolic syndrome (MetS) and the risk of fracture is a matter of debate. OBJECTIVE This work aimed to determine the impact of MetS and its components on the risk of hospitalized fractures, during a median follow-up of 15.9 years. METHODS A total of 7,520 participants (4,068 women) 30 years or older entered the study. Multivariable Cox proportional hazards regression were applied for data analysis. RESULTS The prevalence of MetS was 40.0% and 40.4% in men and women, respectively. During the follow-up, hospitalized fracture was observed in 305 cases (men = 152). The multivariable hazard ratio (HR) and 95% confidence interval (CI) of MetS for incident fracture for men and women was 0.72 (0.49-1.05, P = .08) and 1.38 (0.96-1.98, P = .08), respectively. In the fully adjusted model, high fasting plasma glucose (FPG) among men tended to be associated with a lower risk of fracture [0.67 (0.44-1.02, P = .06)]; among women, high waist circumference (WC) was associated with a greater risk [2.40 (1.55-3.73)]. Among the population 50 years and older in the pooled sample, MetS was not accompanied by the risk of fracture, but high WC was associated with a higher risk [1.58 (1.07-2.33)]. For incident hip/pelvic fracture, abdominal obesity-but not MetS per se-was also a strong and independent risk factor. CONCLUSION A significant sex difference in the association between MetS and its components with incident fracture was observed. Women with central adiposity were at increased risk of hospitalized fracture, whereas men with high FPG were at decreased risk.
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Affiliation(s)
- Atieh Amouzegar
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Samaneh Asgari
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Abbas Momenan
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Farzad Hadaegh
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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González-Hedström D, García-Villalón ÁL, Amor S, de la Fuente-Fernández M, Almodóvar P, Prodanov M, Priego T, Martín AI, Inarejos-García AM, Granado M. Olive leaf extract supplementation improves the vascular and metabolic alterations associated with aging in Wistar rats. Sci Rep 2021; 11:8188. [PMID: 33854149 PMCID: PMC8046982 DOI: 10.1038/s41598-021-87628-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 03/26/2021] [Indexed: 12/29/2022] Open
Abstract
Olive leaves are rich in bioactive substances which exert anti-inflammatory, antioxidant, insulin-sensitizing and antihypertensive effects. The aim of this study was to analyze the possible beneficial effects of an olive leaf extract (OLE) rich in secoiridoids and phenolic compounds on the aging-induced metabolic and vascular alterations. Three experimental groups of rats were used: 3-month-old rats, 24-month-old rats and 24-month-old rats supplemented 21 days with OLE (100 mg/kg). Administration of OLE to aged rats decreased the weight of adrenal glands and prevented the aging-induced loss of body weight and muscle mass. In the serum, OLE reduced the circulating levels of LDL-cholesterol and IL-6 and increased the concentrations of leptin and adiponectin. In the liver OLE attenuated the decreased gene expression of SOD-1, GSR, GCK and GSK-3β and reduced the aging-induced overexpression of NOX-4, Alox-5, iNOS and TNF-α. In aorta segments, OLE prevented endothelial dysfunction and vascular insulin resistance and improved vasoconstriction in response to KCl and NA. Improvement in vascular function was associated with the attenuation of the alterations in the gene expression of COX-2, IL-6, GPx, NOX-1 and IL-10. In conclusion, OLE exerts anti-inflammatory and antioxidant effects in aged rats and attenuates the alterations in vascular function associated with aging.
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Affiliation(s)
- Daniel González-Hedström
- Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
- Pharmactive Biotech Products S.L. Parque Científico de Madrid, Avenida del Doctor Severo Ochoa, 37 Local 4J, Alcobendas, 28108, Madrid, Spain
| | | | - Sara Amor
- Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
| | | | - Paula Almodóvar
- Pharmactive Biotech Products S.L. Parque Científico de Madrid, Avenida del Doctor Severo Ochoa, 37 Local 4J, Alcobendas, 28108, Madrid, Spain
| | - Marin Prodanov
- Departamento de Química Física Aplicada, Facultad de Ciencias, CIAL (CEI, CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain
| | - Teresa Priego
- Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - Ana Isabel Martín
- Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - Antonio Manuel Inarejos-García
- Pharmactive Biotech Products S.L. Parque Científico de Madrid, Avenida del Doctor Severo Ochoa, 37 Local 4J, Alcobendas, 28108, Madrid, Spain
| | - Miriam Granado
- Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
- Instituto de Salud Carlos III, CIBER Fisiopatología de La Obesidad Y Nutrición, Madrid, Spain.
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Chen X, Zhang J, Zhou Z. Changes in Bone Mineral Density After Weight Loss Due to Metabolic Surgery or Lifestyle Intervention in Obese Patients. Obes Surg 2020; 31:1147-1157. [PMID: 33145717 DOI: 10.1007/s11695-020-05095-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 10/27/2020] [Accepted: 10/28/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE Metabolic surgery and lifestyle intervention are two common methods used to treat obesity, but the effects of weight loss on bone mineral density (BMD) remain controversial. Our aim was to evaluate changes in BMD of the total hip, femoral neck, and lumbar spine after weight loss caused by metabolic surgery or lifestyle intervention. MATERIALS AND METHODS We searched PubMed, Web of Science, and the Cochrane Library to identify relevant studies published before 5 August 2020. The primary outcomes, including the BMD of the total hip, femoral neck, and lumbar spine before and 12 months after metabolic surgery or lifestyle intervention, were extracted. RESULTS A total of 19 studies with 1095 participants with obesity were included. Among them, 603 participants with obesity accepted metabolic surgery, while 492 accepted lifestyle intervention. At 12 months after weight loss, the BMD of the total hip decreased significantly in obese patients (mean difference [MD] = 0.06 g/cm2; 95% confidence interval [CI] 0.03 to 0.08; I2 = 67%; P < 0.001), while the BMD of the lumbar spine did not significantly change (P > 0.05). In the subgroup analysis, the BMD of the femoral neck decreased significantly at 12 months in obese patients who underwent metabolic surgery (MD = 0.08 g/cm2; 95% CI 0.04 to 0.13; I2 = 84%; P < 0.001), while it did not significantly change in obese patients who underwent lifestyle treatment (P > 0.05). CONCLUSION Regardless of whether the patients underwent metabolic surgery or lifestyle treatment, the BMD of the total hip significantly decreased in obese patients after weight loss. Different methods used to lose weight may have different effects on the BMD of the femoral neck. Prospective studies, preferably randomized controlled trials (RCTs), are still required to investigate whether the effects of the two treatments on bone metabolism are truly different.
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Affiliation(s)
- Xi Chen
- National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Jingjing Zhang
- National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
| | - Zhiguang Zhou
- National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
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Luo H, Wu H, Tan X, Ye Y, Huang L, Dai H, Mei L. Osteopenic effects of high-fat diet-induced obesity on mechanically induced alveolar bone remodeling. Oral Dis 2020; 27:1243-1256. [PMID: 32989808 DOI: 10.1111/odi.13651] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 08/20/2020] [Accepted: 09/07/2020] [Indexed: 11/27/2022]
Abstract
OBJECTIVES The aim of the study was to investigate the effect of obesity on the tissue and molecular reactions of alveolar bone in response to orthodontic force and its underlying mechanisms. METHODS Sixty-four rats were randomly divided into normal diet (ND) and high-fat diet (HFD) groups for eight weeks of dietary treatment. OTM was induced using nickel-titanium springs between the upper left first molar and incisor. After 1, 3, 7, and 14 days of OTM, the maxillary alveolar bone and gingival tissues were harvested and analyzed. RESULTS Compared with the ND rats, the HFD rats had greater OTM distance, serum levels of tartrate-resistant acid phosphatase (TRAP), and tumor necrosis factor α (TNF-α), as well as significant alveolar bone loss and bone architecture deterioration on both the compression and tension sides (p < .05 for all). This response was linked to the increased osteoclast numbers and functional activity and decreased osteoblast activity in the periodontal ligament, gingival tissue, and alveolar bone. CONCLUSIONS HFD-induced obesity promoted mechanically induced alveolar bone remodeling and detrimental changes in alveolar bone microstructure by increasing osteoclastogenesis and regulating inflammatory cytokine expression. The increased alveolar bone remodeling in the obese rats lead to an accelerated OTM.
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Affiliation(s)
- Hong Luo
- Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China.,Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Hongyan Wu
- Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China.,Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Xi Tan
- Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China.,Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Yusi Ye
- Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China.,Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Lan Huang
- Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China.,Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Hongwei Dai
- Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China.,Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Li Mei
- Department of Oral Sciences, Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
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Abstract
The vertebrate body plan is characterized by the presence of a segmented spine along its main axis. Here, we examine the current understanding of how the axial tissues that are formed during embryonic development give rise to the adult spine and summarize recent advances in the field, largely focused on recent studies in zebrafish, with comparisons to amniotes where appropriate. We discuss recent work illuminating the genetics and biological mechanisms mediating extension and straightening of the body axis during development, and highlight open questions. We specifically focus on the processes of notochord development and cerebrospinal fluid physiology, and how defects in those processes may lead to scoliosis.
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Affiliation(s)
- Michel Bagnat
- Department of Cell Biology, Duke University, Durham, NC, 27710, USA
| | - Ryan S Gray
- Department of Nutritional Sciences, University of Texas at Austin, Dell Pediatrics Research Institute, Austin, TX, 78723, USA
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Roux-en-Y gastric bypass and gastric sleeve surgery result in long term bone loss. Int J Obes (Lond) 2020; 45:235-246. [PMID: 32848203 DOI: 10.1038/s41366-020-00660-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Revised: 07/14/2020] [Accepted: 08/15/2020] [Indexed: 01/01/2023]
Abstract
OBJECTIVES Little is known about the long-term skeletal impact of bariatric procedures, particularly the increasingly commonly performed gastric sleeve surgery (GS). We examined bone density (BMD) change following three types of bariatric surgery Roux-en-Y gastric bypass (RYGB), GS and laparoscopic adjustable gastric banding (LAGB), compared with diet, over 36 months. METHODS Non-randomized, prospective study of participants with severe obesity (n = 52), undergoing weight-loss interventions: RYGB (n = 7), GS (n = 21), LAGB (n = 11) and diet (n = 13). Measurements of calciotropic indices, gut hormones (fasting and post prandial) peptide YY (PYY), glucagon-like peptide 1 (GLP1) and adiponectin together with dual-X-ray absorptiometry and quantitative computed tomography scans were performed thorough the study. RESULTS All groups lost weight during the first 12 months. Despite weight stability from 12 to 36 months and supplementation of calcium and vitamin D, there was progressive bone loss at the total hip (TH) over 36 months in RYGB -14% (95% CI: -12, -17) and GS -9% (95% CI: -7, -10). In RYGB forearm BMD also declined over 36 months -9% (95% CI: -6, -12) and LS BMD declined over the first 12 months -7% (95% CI: -3, -12). RYGB and GS groups experienced significantly greater bone loss until 36 months than LAGB and diet groups, which experienced no significant BMD loss. These bone losses remained significant after adjustment for weight loss and age. RYGB and GS procedures resulted in elevated postprandial PYY, adiponectin and bone turnover markers up to 36 months without such changes among LAGB and diet participants. CONCLUSIONS RYGB and GS but not LAGB resulted in ongoing TH bone loss for three postoperative years. For RYGB, bone loss was also observed at LS and non-weight-bearing forearms. These BMD changes were independent of weight and age differences. We, therefore, recommend close monitoring of bone health following RYGB and GS surgeries.
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Luo J, Dou L, Yang Z, Zhou Z, Huang H. CBFA2T2 promotes adipogenic differentiation of mesenchymal stem cells by regulating CEBPA. Biochem Biophys Res Commun 2020; 529:133-139. [PMID: 32703401 DOI: 10.1016/j.bbrc.2020.05.120] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 05/16/2020] [Indexed: 12/28/2022]
Abstract
The unique metabolic characteristics and diverse functions of marrow adipose tissue (MAT) have drawn more attention recently. Previously, we have reported that CBFA2T2 is required for BMP2-induced osteogenic differentiation of mesenchymal stem/stromal cells (MSCs). In the present study, we further investigated the role of CBFA2T2 in regulation of adipogenic differentiation in mouse bone marrow-derived MSCs (mBMSCs) and human dental pulp stem cells (hDPSCs). We found CBFA2T2 expression was dramatically upregulated during adipogenesis of mBMSCs and hDPSCs. More importantly, knockdown of CBFA2T2 in mBMSCs and hDPSCs significantly inhibited the process of adipogenic differentiation, as revealed by the expression of adipogenic markers and Oil Red O staining. Mechanistically, we found knockdown of CBFA2T2 led to an increase in H3K9me2 and H3K9me3 levels at promoter of CEBPA, an essential transcription factor of adipogenesis. Taken together, these findings suggest CBFA2T2 is key regulator of adipogenic differentiation of MSCs, and it may represent a therapeutic target for conditions with excessive MAT.
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Affiliation(s)
- Jun Luo
- Stomatological Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Lei Dou
- Stomatological Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Zhengyan Yang
- Stomatological Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Zhi Zhou
- Stomatological Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Hong Huang
- Stomatological Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.
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Can Periodontal Disease Be Considered Linked to Obesity and Lipoinflammation? Mechanisms Involved in the Pathogenesis Occurrence. Clin Rev Bone Miner Metab 2020. [DOI: 10.1007/s12018-020-09273-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AbstractObesity is a systemic disease, associated with an increased risk of cardiovascular disorders, type 2 diabetes, cancer, asthma, and osteoarthritis. Overweight and obesity have been suggested to be associated with periodontitis as published in studies and narrative summaries. Obesity and periodontal diseases are very prevalent in the world, and both can lead to severe chronic health conditions and impair people’s life quality. Knowledge of how immune mechanisms and inflammatory responses are regulated is critical for understanding the pathogenesis of complex diseases, such as periodontitis. In conditions of overweight, it has been demonstrated that approximately 70–80% of individuals present an adipose tissue turnover that is both structurally and functionally causing of the systemic inflammatory reaction. The objective of this review is to explore the influence of lipoinflammation. The effects of lipoinflammation and obesity on development of periodontal disease are reported together with the exploration of the mechanisms of interaction between these two diseases.
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Gioia C, Lucchino B, Tarsitano MG, Iannuccelli C, Di Franco M. Dietary Habits and Nutrition in Rheumatoid Arthritis: Can Diet Influence Disease Development and Clinical Manifestations? Nutrients 2020; 12:nu12051456. [PMID: 32443535 PMCID: PMC7284442 DOI: 10.3390/nu12051456] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 05/14/2020] [Accepted: 05/14/2020] [Indexed: 12/14/2022] Open
Abstract
Rheumatoid arthritis (RA) is a systemic, autoimmune disease characterized by joint involvement, with progressive cartilage and bone destruction. Genetic and environmental factors determine RA susceptibility. In recent years, an increasing number of studies suggested that diet has a central role in disease risk and progression. Several nutrients, such as polyunsaturated fatty acids, present anti-inflammatory and antioxidant properties, featuring a protective role for RA development, while others such as red meat and salt have a harmful effect. Gut microbiota alteration and body composition modifications are indirect mechanisms of how diet influences RA onset and progression. Possible protective effects of some dietary patterns and supplements, such as the Mediterranean Diet (MD), vitamin D and probiotics, could be a possible future adjunctive therapy to standard RA treatment. Therefore, a healthy lifestyle and nutrition have to be encouraged in patients with RA.
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Affiliation(s)
- Chiara Gioia
- Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari-Reumatologia, Sapienza University of Rome, 00161 Roma, Italy; (C.G.); (C.I.); (M.D.F.)
| | - Bruno Lucchino
- Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari-Reumatologia, Sapienza University of Rome, 00161 Roma, Italy; (C.G.); (C.I.); (M.D.F.)
- Correspondence: ; Tel.: +39-06-4997-4635
| | | | - Cristina Iannuccelli
- Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari-Reumatologia, Sapienza University of Rome, 00161 Roma, Italy; (C.G.); (C.I.); (M.D.F.)
| | - Manuela Di Franco
- Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari-Reumatologia, Sapienza University of Rome, 00161 Roma, Italy; (C.G.); (C.I.); (M.D.F.)
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Polito R, Monda V, Nigro E, Messina A, Di Maio G, Giuliano MT, Orrù S, Imperlini E, Calcagno G, Mosca L, Mollica MP, Trinchese G, Scarinci A, Sessa F, Salerno M, Marsala G, Buono P, Mancini A, Monda M, Daniele A, Messina G. The Important Role of Adiponectin and Orexin-A, Two Key Proteins Improving Healthy Status: Focus on Physical Activity. Front Physiol 2020; 11:356. [PMID: 32390865 PMCID: PMC7188914 DOI: 10.3389/fphys.2020.00356] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 03/27/2020] [Indexed: 12/15/2022] Open
Abstract
Exercise represents the most important integrative therapy in metabolic, immunologic and chronic diseases; it represents a valid strategy in the non-pharmacological intervention of lifestyle linked diseases. A large body of evidence indicates physical exercise as an effective measure against chronic non-communicable diseases. The worldwide general evidence for health benefits are both for all ages and skill levels. In a dysregulated lifestyle such as in the obesity, there is an imbalance in the production of different cytokines. In particular, we focused on Adiponectin, an adipokine producted by adipose tissue, and on Orexin-A, a neuropeptide synthesized in the lateral hypothalamus. The production of both Adiponectin and Orexin-A increases following regular and structured physical activity and both these hormones have similar actions. Indeed, they improve energy and glucose metabolism, and also modulate energy expenditure and thermogenesis. In addition, a relevant biological role of Adiponectin and Orexin A has been recently highlighted in the immune system, where they function as immune-suppressor factors. The strong connection between these two cytokines and healthy status is mediated by physical activity and candidates these hormones as potential biomarkers of the beneficial effects induced by physical activity. For these reasons, this review aims to underly the interconnections among Adiponectin, Orexin-A, physical activity and healthy status. Furthermore, it is analyzed the involvement of Adiponectin and Orexin-A in physical activity as physiological factors improving healthy status through physical exercise.
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Affiliation(s)
- Rita Polito
- Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, University of Campania "Luigi Vanvitelli", Caserta, Italy.,Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
| | - Vincenzo Monda
- Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana e Unità di Dietetica e Medicina dello Sport, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Ersilia Nigro
- Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, University of Campania "Luigi Vanvitelli", Caserta, Italy.,Ceinge Biotecnologie Avanzate S. C. a R. L., Naples, Italy
| | - Antonietta Messina
- Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana e Unità di Dietetica e Medicina dello Sport, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Girolamo Di Maio
- Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana e Unità di Dietetica e Medicina dello Sport, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Maria Teresa Giuliano
- Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana e Unità di Dietetica e Medicina dello Sport, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Stefania Orrù
- Dipartimento di Scienze Motorie e del Benessere, Università degli Studi di Napoli "Parthenope", Naples, Italy.,IRCCS SDN, Naples, Italy
| | | | - Giuseppe Calcagno
- Dipartimento di Medicina e Scienze della Salute "Vincenzo Tiberio", Università degli Studi del Molise, Campobasso, Italy
| | - Laura Mosca
- Dipartimento di Biologia, Universitá degli studi di Napoli Federico II, Naples, Italy
| | - Maria Pina Mollica
- Dipartimento di Biologia, Universitá degli studi di Napoli Federico II, Naples, Italy
| | - Giovanna Trinchese
- Dipartimento di Biologia, Universitá degli studi di Napoli Federico II, Naples, Italy
| | - Alessia Scarinci
- Dipartimento di Scienze della Formazione, Psicologia, Comunicazione, Università degli Studi di Bari Aldo Moro, Bari, Italy
| | - Francesco Sessa
- Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
| | - Monica Salerno
- Department of Medical, Surgery Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Catania, Italy
| | - Gabriella Marsala
- Struttura Complessa di Farmacia, Azienda Ospedaliero Universitaria - Ospedali Riuniti, Foggia, Italy
| | - Pasqualina Buono
- Ceinge Biotecnologie Avanzate S. C. a R. L., Naples, Italy.,Dipartimento di Scienze Motorie e del Benessere, Università degli Studi di Napoli "Parthenope", Naples, Italy.,IRCCS SDN, Naples, Italy
| | - Annamaria Mancini
- Ceinge Biotecnologie Avanzate S. C. a R. L., Naples, Italy.,Dipartimento di Scienze Motorie e del Benessere, Università degli Studi di Napoli "Parthenope", Naples, Italy
| | - Marcellino Monda
- Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana e Unità di Dietetica e Medicina dello Sport, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Aurora Daniele
- Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, University of Campania "Luigi Vanvitelli", Caserta, Italy.,Ceinge Biotecnologie Avanzate S. C. a R. L., Naples, Italy
| | - Giovanni Messina
- Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
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Shahen VA, Gerbaix M, Koeppenkastrop S, Lim SF, McFarlane KE, Nguyen ANL, Peng XY, Weiss NB, Brennan-Speranza TC. Multifactorial effects of hyperglycaemia, hyperinsulinemia and inflammation on bone remodelling in type 2 diabetes mellitus. Cytokine Growth Factor Rev 2020; 55:109-118. [PMID: 32354674 DOI: 10.1016/j.cytogfr.2020.04.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 04/08/2020] [Indexed: 12/14/2022]
Abstract
Bones undergo continuous cycles of bone remodelling that rely on the balance between bone formation and resorption. This balance allows the bone to adapt to changes in mechanical loads and repair microdamages. However, this balance is susceptible to upset in various conditions, leading to impaired bone remodelling and abnormal bones. This is usually indicated by abnormal bone mineral density (BMD), an indicator of bone strength. Despite this, patients with type 2 diabetes mellitus (T2DM) exhibit normal to high BMD, yet still suffer from an increased risk of fractures. The activity of the bone cells is also altered as indicated by the reduced levels of bone turnover markers in T2DM observed in the circulation. The underlying mechanisms behind these skeletal outcomes in patients with T2DM remain unclear. This review summarises recent findings regarding inflammatory cytokine factors associated with T2DM to understand the mechanisms involved and considers potential therapeutic interventions.
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Affiliation(s)
- V A Shahen
- Department of Physiology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Australia
| | - M Gerbaix
- Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva, Switzerland
| | - S Koeppenkastrop
- Department of Physiology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Australia
| | - S F Lim
- Department of Physiology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Australia
| | - K E McFarlane
- Department of Physiology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Australia
| | - Amanda N L Nguyen
- Department of Physiology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Australia
| | - X Y Peng
- Department of Physiology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Australia
| | - N B Weiss
- Department of Physiology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Australia
| | - T C Brennan-Speranza
- Department of Physiology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Australia; School of Public Health, Faculty of Medicine and Health, The University of Sydney, Australia.
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50
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Sun LN, Liu XL. Functions of adiponectin signaling in regulating neural plasticity and its application as the therapeutic target to neurological and psychiatric diseases. Rev Neurosci 2020; 30:485-495. [PMID: 30864396 DOI: 10.1515/revneuro-2018-0062] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 10/06/2018] [Indexed: 12/15/2022]
Abstract
Convergent lines of evidence indicate the critical roles of adiponectin in regulating neural functions on different levels. Because of the importance in maintaining neural plasticity including adult neurogenesis and synaptic plasticity, adiponectin has the potential to serve as the treatment targets in therapies of neurological and psychiatric disorders. Hence, systematic review is needed to summarize how adiponectin works in the brain, and how the adiponectin pathway is employed as the treatment method needs to be determined. Moreover, the benefits of adiponectin as the regulator for neural plasticity such as synaptic plasticity and neurogenesis have been supported by many literatures. In the current article, we reviewed the functions of adiponectin in different types of neural plasticity. We also demonstrated the potential value of adiponectin as the treatment target for different types of neurodegenerative and psychiatric disorders. Taken together, this review offers a new insight about adiponectin as the ideal target to develop the new treatment methods against neurodegeneration or psychiatric diseases.
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Affiliation(s)
- Li-Na Sun
- School of PE and Sport, Beijing Normal University, Beijing 100875, China
| | - Xiao-Li Liu
- School of PE and Sport, Beijing Normal University, Beijing 100875, China
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