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Khan MA, Khan MA, Siddiqui S, Misra A, Yadav K, Srivastava A, Trivedi A, Husain I, Ahmad R. Phytoestrogens as potential anti-osteoporosis nutraceuticals: Major sources and mechanism(s) of action. J Steroid Biochem Mol Biol 2025; 251:106740. [PMID: 40139537 DOI: 10.1016/j.jsbmb.2025.106740] [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: 01/07/2025] [Revised: 03/04/2025] [Accepted: 03/18/2025] [Indexed: 03/29/2025]
Abstract
By 2050, the global aging population is predicted to reach 1.5 billion, highlighting the need to enhance the quality of life of the elderly population. Osteoporotic fractures are projected to affect one in three women and one in five men over age 50. Initial treatments for osteoporosis in postmenopausal women include antiresorptive agents such as bisphosphonates, strontium ranelate, estrogen replacement therapy (ERT) and selective estrogen receptor modulators (SERMs). However, these do not rebuild bone, limiting their effectiveness. Denosumab, an FDA-approved antiresorptive monoclonal antibody, also has drawbacks including high costs, biannual subcutaneous injections, slow healing, impaired bone growth and side effects like eczema, flatulence, cellulitis, osteonecrosis of the jaw (ONJ) and an increased risk of spinal fractures after discontinuation of treatment. Nutraceuticals, particularly phytoestrogens, are gaining attention for their health benefits and safety in osteoporosis prevention, management and treatment. Phytoestrogens are plant metabolites similar to mammalian estrogens and include isoflavones, coumestans, lignans, stilbenes, and flavonoids. They interact with estrogen receptor isoforms ERα and ERβ, acting as agonists or antagonists based on concentration and bioavailability. Their tissue-selective activities are particularly significant: anti-estrogenic effects in reproductive tissues may lower the risk of hormone-related cancers (such as ovarian, uterine, breast and prostate), while estrogenic effects on bone could contribute to the preservation of bone mineral density.Phytoestrogens are, thus, used in managing breast and prostate cancers, cardiovascular diseases, menopause and osteoporosis. The present review focuses on the botanical origin, classification, sources and mechanism(s) of action of major phytoestrogens, their potential in prevention and management of osteoporosis and the requirement for additional clinical trials to achieve more definitive outcomes in order to confirm their efficacy and dosage safety.
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Affiliation(s)
- Mohammad Amir Khan
- Dept. of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Hardoi Road, Lucknow, UP 226003, India
| | - Mohsin Ali Khan
- Dept. of Research & Development, Era University, Lucknow, UP 226003, India
| | - Sahabjada Siddiqui
- Dept. of Biotechnology, Era's Lucknow Medical College & Hospital, Era University, Sarfarazganj, Hardoi Road, Lucknow, UP 226003, India
| | - Aparna Misra
- Dept. of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Hardoi Road, Lucknow, UP 226003, India
| | - Kusum Yadav
- Dept. of Biochemistry, University of Lucknow, Lucknow, UP 226003, India
| | - Aditi Srivastava
- Dept. of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Hardoi Road, Lucknow, UP 226003, India
| | - Anchal Trivedi
- Dept. of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Hardoi Road, Lucknow, UP 226003, India
| | - Ishrat Husain
- Dept. of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Hardoi Road, Lucknow, UP 226003, India
| | - Rumana Ahmad
- Dept. of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Hardoi Road, Lucknow, UP 226003, India.
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Aly Abdelfattah MT, Kassem AA, Mohamed Shalaby HK, Awad Tantawy MA. Investigation of the effect of resveratrol lyo-nanograft on the bone regeneration process of osseous bony defects in rabbits. Int J Pharm 2025; 678:125679. [PMID: 40324606 DOI: 10.1016/j.ijpharm.2025.125679] [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: 01/29/2025] [Revised: 05/01/2025] [Accepted: 05/01/2025] [Indexed: 05/07/2025]
Abstract
Periodontal diseases affect tooth-supporting structure producing bone-defects. Well-known bone-regeneration techniques are expensive, sophisticated and maybe immunogenic. We aimed at emerging a cost-effective, easily manufactured and safe nano-bone graft containing the natural-polyphenol resveratrol (RSV) which was reported to have in-vivo bone-regeneration efficacy. However, RSV suffers from poor solubility, bioavailability and photosensitivity. Its incorporation into a nanocarrier system could resolve these problems. RSV liposomes were prepared using Phosal® in different ratios and the optimized formula showed multilamellar vesicles, PS (126.1 nm), PDI (0.3017), ZP (-34.5 mV), %EE (90.86 %), with a sustained-release pattern. Then it was lyophilized and recharacterized and the obtained pliable mass (RSV-Ph75-LyoMan) lyo-nanograft suited its application into bone-defects performed in rabbits' tibiae. Histomorphometric quantitative analyses of bone sections micrographs were performed to verify RSV anti-inflammatory action, by counting bone marrow-infiltrating lymphocytes, and to explore the phases of bone-regeneration process exerted by RSV, by counting osteocytes, osteoblasts and osteoclasts and further confirmed by assessing bone-thickness, using ImageJ-software. This was done after 3, 6, 9 weeks of applying either placebo or RSV-Ph75-LyoMan. A significant decrease in lymphocytes' counts in RSV-Ph75-LyoMan compared to control-sites at the assessed time points was obtained. Further, RSV-Ph75-LyoMan significantly accelerated bone-healing and regeneration processes as concluded from the differential osteocytes, osteoblasts and osteoclasts counts. Consequently, a significant increase in bone-thickness in (RSV-Ph75-LyoMan)-treated-sites; 68.25 ± 3.45, 109.5 ± 5.49, and 148.2 ± 7.25 µm after 3, 6, 9 weeks was obtained, with a significant difference when compared to control-sites; 40.05 ± 2.21, 45.23 ± 1.87 and 46.57 ± 1.45 µm, respectively. Histological studies confirmed trabecular-remolding after 9 weeks in (RSV-Ph75-LyoMan)-treated-sites. RSV-Ph75-LyoMan lyo-nanograft is promising for treatment of osseous bony-defects in rabbits.
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Affiliation(s)
| | - Abeer Ahmed Kassem
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
| | | | - Mohamed Ali Awad Tantawy
- Department of Oral Medicine and Periodontology, Faculty of Dentistry, Suez Canal University, Ismailia, Egypt
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Chen X, Huang X, Zhang X, Chen Z. Metabolism-epigenetic interaction-based bone and dental regeneration: From impacts and mechanisms to treatment potential. Bone 2025; 192:117382. [PMID: 39730093 DOI: 10.1016/j.bone.2024.117382] [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: 09/05/2024] [Revised: 12/11/2024] [Accepted: 12/23/2024] [Indexed: 12/29/2024]
Abstract
Metabolic pathways exhibit fluctuating activities during bone and dental loss and defects, suggesting a regulated metabolic plasticity. Skeletal remodeling is an energy-demanding process related to altered metabolic activities. These metabolic changes are frequently associated with epigenetic modifications, including variations in the expression or activity of enzymes modified through epigenetic mechanisms, which directly or indirectly impact cellular metabolism. Metabolic reprogramming driven by bone and dental conditions alters the epigenetic landscape by modulating the activities of DNA and histone modification enzymes at the metabolite level. Epigenetic mechanisms modulate the expression of metabolic genes, consequently influencing the metabolome. The interplay between epigenetics and metabolomics is crucial in maintaining bone and dental homeostasis by preserving cell proliferation and pluripotency. This review, therefore, aims to examine the effects of metabolic reprogramming in bone and dental-related cells on the regulation of epigenetic modifications, particularly acetylation, methylation, and lactylation. We also discuss the effects of chromatin-modifying enzymes on metabolism and the potential therapeutic benefits of dietary compounds as epigenetic modulators. In this review, we highlight the inconsistencies in current research findings and suggest potential approaches to translate fundamental insights into clinical treatments for bone and tooth diseases.
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Affiliation(s)
- Xinyi Chen
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Centre for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Centre of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China
| | - Xiaoyuan Huang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Centre for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Centre of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China
| | - Xiatong Zhang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Centre for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Centre of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China
| | - Zhuo Chen
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Centre for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Centre of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China.
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4
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Bojtor B, Balla B, Vaszilko M, Szentpeteri S, Putz Z, Kosa JP, Lakatos P. Genetic Background of Medication-Related Osteonecrosis of the Jaw: Current Evidence and Future Perspectives. Int J Mol Sci 2024; 25:10488. [PMID: 39408816 PMCID: PMC11477157 DOI: 10.3390/ijms251910488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 09/19/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, VEGFA, and CYP2C8. With the development of molecular biology, newer methods such as miRNA and gene expression studies have been introduced in MRONJ, in addition to methods that can examine the base sequence of the DNA. Describing the complex genetic background of MRONJ can help further understand its pathophysiology as well as identify new therapeutic targets to better manage this adverse drug reaction.
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Affiliation(s)
- Bence Bojtor
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (B.B.); (Z.P.); (J.P.K.)
| | - Bernadett Balla
- Hungarian Research Network SE-ENDOMOLPAT Research Group, 1085 Budapest, Hungary;
| | - Mihaly Vaszilko
- Department of Oro-Maxillofacial Surgery and Stomatology, Semmelweis University, 1085 Budapest, Hungary; (M.V.); (S.S.)
| | - Szofia Szentpeteri
- Department of Oro-Maxillofacial Surgery and Stomatology, Semmelweis University, 1085 Budapest, Hungary; (M.V.); (S.S.)
| | - Zsuzsanna Putz
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (B.B.); (Z.P.); (J.P.K.)
- Hungarian Research Network SE-ENDOMOLPAT Research Group, 1085 Budapest, Hungary;
| | - Janos P. Kosa
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (B.B.); (Z.P.); (J.P.K.)
- Hungarian Research Network SE-ENDOMOLPAT Research Group, 1085 Budapest, Hungary;
| | - Peter Lakatos
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (B.B.); (Z.P.); (J.P.K.)
- Hungarian Research Network SE-ENDOMOLPAT Research Group, 1085 Budapest, Hungary;
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Chen H, Weng Z, Kalinowska M, Xiong L, Wang L, Song H, Xiao J, Wang F, Shen X. Anti-osteoporosis effect of bioactives in edible medicinal plants: a comprehensive review. Crit Rev Food Sci Nutr 2024:1-17. [PMID: 39093554 DOI: 10.1080/10408398.2024.2386449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
Current treatments for osteoporosis include a calcium-rich diet, adequate exercise, and medication. Many synthetic drugs, although fast-acting, can cause a range of side effects for patients when taken over a long period, such as irritation of the digestive tract and a burden on the kidneys. As the world's population ages, the prevalence of osteoporosis is increasing, and the development of safe and effective treatments is urgently needed. Active compounds in edible and medicinal homologous plants have been used for centuries to improve bone quality. It is possible to employ them as dietary supplements to prevent osteoporosis. In this review, we analyze the influencing factors of osteoporosis and systematically summarize the research progress on the anti-osteoporosis effects of active compounds in edible and medicinal homologous plants. The literature suggests that some naturally occurring active compounds in edible and medicinal homologous plants can inhibit bone loss, prevent the degeneration of bone cell microstructure, and reduce bone fragility through alleviating oxidative stress, regulating autophagy, anti-inflammation, improving gut flora, and regulating estrogen level with little side effects. Our review provides useful guidance for the use of edible and medicinal homologous plants and the development of safer novel anti-osteoporosis dietary supplements.
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Affiliation(s)
- Huiling Chen
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
| | - Zebin Weng
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Monika Kalinowska
- Department of Chemistry, Biology and Biotechnology, Bialystok University of Technology, Bialystok, Poland
| | - Ling Xiong
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
| | - Luanfeng Wang
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
| | - Haizhao Song
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
| | - Jianbo Xiao
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
- Department of Analytical Chemistry and Food Science, Instituto de Agroecoloxía e Alimentación (IAA) - CITEXVI, Universidade de Vigo, Nutrition and Bromatology Group, Vigo, Spain
| | - Fang Wang
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
- Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA
| | - Xinchun Shen
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, China
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Waykar TR, Mandlik SK, Mandlik DS. Sirtuins: exploring next-gen therapeutics in the pathogenesis osteoporosis and associated diseases. Immunopharmacol Immunotoxicol 2024; 46:277-301. [PMID: 38318808 DOI: 10.1080/08923973.2024.2315418] [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: 06/05/2023] [Accepted: 01/30/2024] [Indexed: 02/07/2024]
Abstract
OBJECTIVE Osteoporosis poses a substantial public health challenge due to an ageing population and the lack of adequate treatment options. The condition is marked by a reduction in bone mineral density, resulting in an elevated risk of fractures. The reduction in bone density and strength, as well as musculoskeletal issues that come with aging, present a significant challenge for individuals impacted by these conditions, as well as the healthcare system worldwide. METHODS Literature survey was conducted until May 2023 using databases such as Web of Science, PubMed, Scopus, and Google Scholar. RESULT Sirtuins 1-7 (SIRT1-SIRT7), which are a group of Nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, possess remarkable capabilities to increase lifespan and combat diseases related to aging. Research has demonstrated that these proteins play an important role in regular skeletal development and maintenance by directly impacting bone cells. Their dysfunction could be a factor in various bone conditions. Studies conducted on animals before clinical trials have shown that administering Sirtuins agonists to mice provides a safeguard against osteoporosis resulting from aging, menopause, and immobilization. These findings imply that Sirtuins may be a viable target for addressing the irregularity in bone remodeling and treating osteoporosis and other skeletal ailments. CONCLUSION The purpose of this review was to present a thorough and current evaluation of the existing knowledge on Sirtuins biology, with a particular emphasis on their involvement in maintaining bone homeostasis and contributing to osteoporosis. Additionally, the review examines potential pharmacological interventions targeting Sirtuins for the treatment of osteoporosis.
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Affiliation(s)
- Tejal R Waykar
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Satish K Mandlik
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Deepa S Mandlik
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, India
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Faienza MF, Giardinelli S, Annicchiarico A, Chiarito M, Barile B, Corbo F, Brunetti G. Nutraceuticals and Functional Foods: A Comprehensive Review of Their Role in Bone Health. Int J Mol Sci 2024; 25:5873. [PMID: 38892062 PMCID: PMC11172758 DOI: 10.3390/ijms25115873] [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: 04/03/2024] [Revised: 05/16/2024] [Accepted: 05/24/2024] [Indexed: 06/21/2024] Open
Abstract
Bone health is the result of a tightly regulated balance between bone modeling and bone remodeling, and alterations of these processes have been observed in several diseases both in adult and pediatric populations. The imbalance in bone remodeling can ultimately lead to osteoporosis, which is most often associated with aging, but contributing factors can already act during the developmental age, when over a third of bone mass is accumulated. The maintenance of an adequate bone mass is influenced by genetic and environmental factors, such as physical activity and diet, and particularly by an adequate intake of calcium and vitamin D. In addition, it has been claimed that the integration of specific nutraceuticals such as resveratrol, anthocyanins, isoflavones, lycopene, curcumin, lutein, and β-carotene and the intake of bioactive compounds from the diet such as honey, tea, dried plums, blueberry, and olive oil can be efficient strategies for bone loss prevention. Nutraceuticals and functional foods are largely used to provide medical or health benefits, but there is an urge to determine which products have adequate clinical evidence and a strong safety profile. The aim of this review is to explore the scientific and clinical evidence of the positive role of nutraceuticals and functional food in bone health, focusing both on molecular mechanisms and on real-world studies.
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Affiliation(s)
- Maria Felicia Faienza
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari “A. Moro”, 70124 Bari, Italy; (M.F.F.)
| | - Silvia Giardinelli
- Department of Medical Sciences, Pediatrics, University of Ferrara, 44121 Ferrara, Italy
| | - Alessia Annicchiarico
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy; (A.A.); (B.B.)
| | - Mariangela Chiarito
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari “A. Moro”, 70124 Bari, Italy; (M.F.F.)
| | - Barbara Barile
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy; (A.A.); (B.B.)
| | - Filomena Corbo
- Department of Pharmacy-Drug Sciences, University of Bari “A. Moro”, 70125 Bari, Italy;
| | - Giacomina Brunetti
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy; (A.A.); (B.B.)
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Loukas AT, Papadourakis M, Panagiotopoulos V, Zarmpala A, Chontzopoulou E, Christodoulou S, Katsila T, Zoumpoulakis P, Matsoukas MT. Natural Compounds for Bone Remodeling: A Computational and Experimental Approach Targeting Bone Metabolism-Related Proteins. Int J Mol Sci 2024; 25:5047. [PMID: 38732267 PMCID: PMC11084538 DOI: 10.3390/ijms25095047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 04/25/2024] [Accepted: 04/26/2024] [Indexed: 05/13/2024] Open
Abstract
Osteoporosis, characterized by reduced bone density and increased fracture risk, affects over 200 million people worldwide, predominantly older adults and postmenopausal women. The disruption of the balance between bone-forming osteoblasts and bone-resorbing osteoclasts underlies osteoporosis pathophysiology. Standard treatment includes lifestyle modifications, calcium and vitamin D supplementation and specific drugs that either inhibit osteoclasts or stimulate osteoblasts. However, these treatments have limitations, including side effects and compliance issues. Natural products have emerged as potential osteoporosis therapeutics, but their mechanisms of action remain poorly understood. In this study, we investigate the efficacy of natural compounds in modulating molecular targets relevant to osteoporosis, focusing on the Mitogen-Activated Protein Kinase (MAPK) pathway and the gut microbiome's influence on bone homeostasis. Using an in silico and in vitro methodology, we have identified quercetin as a promising candidate in modulating MAPK activity, offering a potential therapeutic perspective for osteoporosis treatment.
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Affiliation(s)
- Alexandros-Timotheos Loukas
- Department of Food Science and Technology, University of West Attica, Ag. Spyridonos, 12243 Egaleo, Greece; (A.-T.L.); (P.Z.)
- Cloudpharm Private Company, Kifissias Avenue 44, 15125 Marousi, Greece; (V.P.); (A.Z.); (E.C.); (S.C.)
| | - Michail Papadourakis
- Cloudpharm Private Company, Kifissias Avenue 44, 15125 Marousi, Greece; (V.P.); (A.Z.); (E.C.); (S.C.)
| | - Vasilis Panagiotopoulos
- Cloudpharm Private Company, Kifissias Avenue 44, 15125 Marousi, Greece; (V.P.); (A.Z.); (E.C.); (S.C.)
- Department of Biomedical Engineering, University of West Attica, Ag. Spyridonos, 12243 Egaleo, Greece
| | - Apostolia Zarmpala
- Cloudpharm Private Company, Kifissias Avenue 44, 15125 Marousi, Greece; (V.P.); (A.Z.); (E.C.); (S.C.)
| | - Eleni Chontzopoulou
- Cloudpharm Private Company, Kifissias Avenue 44, 15125 Marousi, Greece; (V.P.); (A.Z.); (E.C.); (S.C.)
| | - Stephanos Christodoulou
- Cloudpharm Private Company, Kifissias Avenue 44, 15125 Marousi, Greece; (V.P.); (A.Z.); (E.C.); (S.C.)
| | - Theodora Katsila
- Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece;
| | - Panagiotis Zoumpoulakis
- Department of Food Science and Technology, University of West Attica, Ag. Spyridonos, 12243 Egaleo, Greece; (A.-T.L.); (P.Z.)
- Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece;
| | - Minos-Timotheos Matsoukas
- Cloudpharm Private Company, Kifissias Avenue 44, 15125 Marousi, Greece; (V.P.); (A.Z.); (E.C.); (S.C.)
- Department of Biomedical Engineering, University of West Attica, Ag. Spyridonos, 12243 Egaleo, Greece
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Hwang SM, Kim TY, Kim A, Kim YG, Park JW, Lee JM, Kim JY, Suh JY. Resveratrol facilitates bone formation in high-glucose conditions. Front Physiol 2024; 15:1347756. [PMID: 38706943 PMCID: PMC11066205 DOI: 10.3389/fphys.2024.1347756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 04/05/2024] [Indexed: 05/07/2024] Open
Abstract
Periodontitis is known to be affected by high-glucose conditions, which poses a challenge to periodontal tissue regeneration, particularly in bone formation. In this study, the potential effects of resveratrol (3,5,4'-trihydroxystilbene, RSV) in facilitating bone formation under high-glucose conditions after periodontitis has been investigated. We focused on the analysis of osteoblasts and periodontal ligament cells, which are essential for bone formation including cell proliferation and differentiation. And we aimed to investigate the impact of RSV on bone healing, employed diabetic mouse model induced by streptozotocin and confirmed through histological observation. High-glucose conditions adversely affected cell proliferation and ALP activity in both MC3T3-E1 and hPDLF in vitro, with more significant impact on MC3T3-E1 cells. RSV under high-glucose conditions had positive effects on both, showing early-stage effects for MC3T3-E1 cells and later-stage effects for hPDLF cells. RSV seemed to have a more pronounced rescuing role in MC3T3-E1 cells. Increased ALP activity was observed and the expression levels of significant genes, such as Col 1, TGF-β1, ALP, and OC, in osteogenic differentiation were exhibited stage-specific expression patterns. Upregulated Col 1 and TGF-β1 were detected in the early stage, and then ALP and OC expressions became more pronounced in the later stages. Similarly, stronger positive reactions against RUNX2 were detected in the RSV-treated group compared to the control. Furthermore, in in vivo experiment, RSV stimulates the growth and differentiation of osteoblasts, thereby promoting bone formation. High-glucose levels have the potential to impair cellular functions and the regenerative capacity to facilitate bone formation with MC3T3-E1 rather than hPDLF cells. Resveratrol appears to facilitate the inherent abilities of MC3T3-E1 cells compared with hPDLF cells, indicating its potential capacity to restore functionality during periodontal regeneration.
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Affiliation(s)
- Sung-Min Hwang
- Department of Periodontology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea
| | - Tae-Young Kim
- Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea
| | - Anna Kim
- Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea
| | - Yong-Gun Kim
- Department of Periodontology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea
| | - Jin-Woo Park
- Department of Periodontology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea
| | - Jae-Mok Lee
- Department of Periodontology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea
| | - Jae-Young Kim
- Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea
| | - Jo-Young Suh
- Department of Periodontology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea
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10
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Yi SJ, Lim J, Kim K. Exploring epigenetic strategies for the treatment of osteoporosis. Mol Biol Rep 2024; 51:398. [PMID: 38453825 DOI: 10.1007/s11033-024-09353-4] [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: 12/08/2023] [Accepted: 02/14/2024] [Indexed: 03/09/2024]
Abstract
The worldwide trend toward an aging population has resulted in a higher incidence of chronic conditions, such as osteoporosis. Osteoporosis, a prevalent skeletal disorder characterized by decreased bone mass and increased fracture risk, encompasses primary and secondary forms, each with distinct etiologies. Mechanistically, osteoporosis involves an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Current pharmacological interventions for osteoporosis, such as bisphosphonates, denosumab, and teriparatide, aim to modulate bone turnover and preserve bone density. Hormone replacement therapy and lifestyle modifications are also recommended to manage the condition. While current medications offer therapeutic options, they are not devoid of limitations. Recent studies have highlighted the importance of epigenetic mechanisms, including DNA methylation and histone modifications, in regulating gene expression during bone remodeling. The use of epigenetic drugs, or epidrugs, to target these mechanisms offers a promising avenue for therapeutic intervention in osteoporosis. In this review, we comprehensively examine the recent advancements in the application of epidrugs for treating osteoporosis.
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Affiliation(s)
- Sun-Ju Yi
- Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Jaeho Lim
- Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Kyunghwan Kim
- Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
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11
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Meyer C, Brockmueller A, Buhrmann C, Shakibaei M. Prevention and Co-Management of Breast Cancer-Related Osteoporosis Using Resveratrol. Nutrients 2024; 16:708. [PMID: 38474838 DOI: 10.3390/nu16050708] [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: 02/04/2024] [Revised: 02/21/2024] [Accepted: 02/26/2024] [Indexed: 03/14/2024] Open
Abstract
Breast cancer (BC) is currently one of the most common cancers in women worldwide with a rising tendency. Epigenetics, generally inherited variations in gene expression that occur independently of changes in DNA sequence, and their disruption could be one of the main causes of BC due to inflammatory processes often associated with different lifestyle habits. In particular, hormone therapies are often indicated for hormone-positive BC, which accounts for more than 50-80% of all BC subtypes. Although the cure rate in the early stage is more than 70%, serious negative side effects such as secondary osteoporosis (OP) due to induced estrogen deficiency and chemotherapy are increasingly reported. Approaches to the management of secondary OP in BC patients comprise adjunctive therapy with bisphosphonates, non-steroidal anti-inflammatory drugs (NSAIDs), and cortisone, which partially reduce bone resorption and musculoskeletal pain but which are not capable of stimulating the necessary intrinsic bone regeneration. Therefore, there is a great therapeutic need for novel multitarget treatment strategies for BC which hold back the risk of secondary OP. In this review, resveratrol, a multitargeting polyphenol that has been discussed as a phytoestrogen with anti-inflammatory and anti-tumor effects at the epigenetic level, is presented as a potential adjunct to both support BC therapy and prevent osteoporotic risks by positively promoting intrinsic regeneration. In this context, resveratrol is also known for its unique role as an epigenetic modifier in the regulation of essential signaling processes-both due to its catabolic effect on BC and its anabolic effect on bone tissue.
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Affiliation(s)
- Christine Meyer
- Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Pettenkoferstr. 11, 80336 Munich, Germany
| | - Aranka Brockmueller
- Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Pettenkoferstr. 11, 80336 Munich, Germany
| | - Constanze Buhrmann
- Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Augsburg, 86159 Augsburg, Germany
| | - Mehdi Shakibaei
- Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Pettenkoferstr. 11, 80336 Munich, Germany
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12
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Zhang T, Wang L, Duan X, Niu Y, Li M, Yun L, Sun H, Ma Y, Guo Y. Sirtuins mediate mitochondrial quality control mechanisms: a novel therapeutic target for osteoporosis. Front Endocrinol (Lausanne) 2024; 14:1281213. [PMID: 38264287 PMCID: PMC10805026 DOI: 10.3389/fendo.2023.1281213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 12/01/2023] [Indexed: 01/25/2024] Open
Abstract
Mitochondria plays a role in cell differentiation and apoptosis processes. Maintaining mitochondrial function is critical, and this involves various aspects of mitochondrial quality control such as protein homeostasis, biogenesis, dynamics, and mitophagy. Osteoporosis, a metabolic bone disorder, primarily arises from two factors: the dysregulation between lipogenic and osteogenic differentiation of aging bone marrow mesenchymal stem cells, and the imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Mitochondrial quality control has the potential to mitigate or even reverse the effects. Among the Sirtuin family, consisting of seven Sirtuins (SIRT1-7), SIRT1-SIRT6 play a crucial role in maintaining mitochondrial quality control. Additionally, SIRT1, SIRT3, SIRT6, and SIRT7 are directly involved in normal bone development and homeostasis by modulating bone cells. However, the precise mechanism by which these Sirtuins exert their effects remains unclear. This article reviews the impact of various aspects of mitochondrial quality control on osteoporosis, focusing on how SIRT1, SIRT3, and SIRT6 can improve osteoporosis by regulating mitochondrial protein homeostasis, biogenesis, and mitophagy. Furthermore, we provide an overview of the current state of clinical and preclinical drugs that can activate Sirtuins to improve osteoporosis. Specific Sirtuin-activating compounds are effective, but further studies are needed. The findings of this study may offer valuable insights for future research on osteoporosis and the development of clinical prevention and therapeutic target strategies.
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Affiliation(s)
- Tianchi Zhang
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Lining Wang
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Xiping Duan
- Acupuncture Anesthesia Clinical Research Institute, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yuanyuan Niu
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Muzhe Li
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Li Yun
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Haitao Sun
- Department of Orthopedic, Wuxi Huishan District People’s Hospital, Wuxi, Jiangsu, China
| | - Yong Ma
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Traumatology and Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yang Guo
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Traumatology and Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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13
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Brown K, Theofanous D, Britton RG, Aburido G, Pepper C, Sri Undru S, Howells L. Resveratrol for the Management of Human Health: How Far Have We Come? A Systematic Review of Resveratrol Clinical Trials to Highlight Gaps and Opportunities. Int J Mol Sci 2024; 25:747. [PMID: 38255828 PMCID: PMC10815776 DOI: 10.3390/ijms25020747] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/01/2024] [Accepted: 01/03/2024] [Indexed: 01/24/2024] Open
Abstract
Resveratrol has long been proposed as being beneficial to human health across multiple morbidities, yet there is currently no conclusive clinical evidence to advocate its recommendation in any healthcare setting. A large cohort with high-quality clinical data and clearly defined biomarkers or endpoints are required to draw meaningful conclusions. This systematic review compiles every clinical trial conducted using a defined dose of resveratrol in a purified form across multiple morbidities to highlight the current 'state-of-play' and knowledge gaps, informing future trial designs to facilitate the realisation of resveratrol's potential benefits to human health. Over the last 20 years, there have been almost 200 studies evaluating resveratrol across at least 24 indications, including cancer, menopause symptoms, diabetes, metabolic syndrome, and cardiovascular disease. There are currently no consensus treatment regimens for any given condition or endpoint, beyond the fact that resveratrol is generally well-tolerated at a dose of up to 1 g/day. Additionally, resveratrol consistently reduces inflammatory markers and improves aspects of a dysregulated metabolism. In conclusion, over the last 20 years, the increasing weight of clinical evidence suggests resveratrol can benefit human health, but more large, high-quality clinical trials are required to transition this intriguing compound from health food shops to the clinic.
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Affiliation(s)
- Karen Brown
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
| | - Despoina Theofanous
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
| | - Robert G. Britton
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
| | - Grandezza Aburido
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
| | - Coral Pepper
- Odames Library, Victoria Building, Leicester Royal Infirmary, Leicester LE1 5WW, UK
| | - Shanthi Sri Undru
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
| | - Lynne Howells
- Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK; (D.T.); (R.G.B.); (G.A.); (S.S.U.); (L.H.)
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14
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Chopane S, Chaudhry K, Kohli A, Singh S, Banerjee M, Kumar P, Ganesan A, Chugh A. Safety and Efficacy of Resveratrol in Healing of Maxillofacial Fractures: A Randomized Controlled Study. J Maxillofac Oral Surg 2023; 22:987-994. [PMID: 38105826 PMCID: PMC10719438 DOI: 10.1007/s12663-023-01992-7] [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: 01/06/2023] [Accepted: 08/05/2023] [Indexed: 12/19/2023] Open
Abstract
Objectives To assess the efficacy of resveratrol in improving functional outcomes following open reduction and internal fixation of maxillofacial fractures. Study Design A single-center, randomized, parallel group, prospective, double-blind clinical trial was conducted on 40 patients between the age 20 and 60 years, requiring open reduction and internal fixation of maxillofacial fractures. The selected patients were randomly divided into two groups, Group 1 (placebo) and Group 2 (resveratrol) where tablets resveratrol 500 mg were given twice daily for 1 month following open reduction and internal fixation of fractured segments. Bite force was calculated pre-operatively and on the 1st, 4th, 8th and 12th week postoperatively. Serum markers osteocalcin and alkaline phosphate were calculated pre-operatively and at 4th and 12th week postoperatively. Results Bite force (690.55 ± 262.00) in the resveratrol group was higher than the placebo group (553.27 ± 300.08) at 12th week postoperatively. However, the difference was non-significant statistically (p = 0.132). Resveratrol group (116.80 ± 55.25) showed better maintenance of serum ALP level as compared to placebo group (107.90 ± 42.99) at 12th week postoperatively, but again it lacked statistical significance (p = 0.573). Resveratrol group after initial reduction at 4th week showed serum osteocalcin levels nearly equal to the preoperative values at 12th week, while the placebo group showed a decline both at 4th and 12th week postoperatively. However, these results were not statistically significant (p = 0.065). Conclusion There was no statistically significant difference in bite force, serum ALP level and serum osteocalcin levels between placebo group and resveratrol group. Though not statistically significant but early increased level of serum osteogenic markers, better restoration of bite force in group 2 (tab. Resveratrol) indicates toward its possible optimistic role in maxillofacial fracture healing. More studies with larger sample sizes are needed in order to confirm the efficacy of this drug in maxillofacial fracture.
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Affiliation(s)
- Shivkumar Chopane
- Department of Oral and Maxillofacial Surgery, All India Institute of Medical Sciences, Jodhpur, India
| | - Kirti Chaudhry
- Oral and Maxillofacial Surgery, Department of Dentistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Aakash Kohli
- Oral and Maxillofacial Surgery, Department of Dentistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Surjit Singh
- Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India
| | - Mithu Banerjee
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Pravin Kumar
- Department of Dentistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Aparna Ganesan
- Department of Oral and Maxillofacial Surgery, All India Institute of Medical Sciences, Jodhpur, India
| | - Ankita Chugh
- Oral and Maxillofacial Surgery, Department of Dentistry, All India Institute of Medical Sciences, Jodhpur, India
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15
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Ostos Mendoza KC, Garay Buenrostro KD, Kanabar PN, Maienschein-Cline M, Los NS, Arbieva Z, Raut NA, Lawal TO, López AM, Cabada-Aguirre P, Luna-Vital DA, Mahady GB. Peonidin-3- O-glucoside and Resveratrol Increase the Viability of Cultured Human hFOB Osteoblasts and Alter the Expression of Genes Associated with Apoptosis, Osteoblast Differentiation and Osteoclastogenesis. Nutrients 2023; 15:3233. [PMID: 37513651 PMCID: PMC10383121 DOI: 10.3390/nu15143233] [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: 06/08/2023] [Revised: 07/10/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023] Open
Abstract
High-throughput RNA-sequencing can determine the impact of nutrients and their combinations on gene transcription levels in osteocytes, and clarify the biological pathways associated with their impact on bone tissues. Previously, we reported that resveratrol (RES) and peonidin-3-O-glucoside (POG) increased osteoblastogenesis, as well as reduced osteoclastogenesis in transgenic teleost fish models. Here, we perform whole-genome transcriptomic profiling of osteoblasts treated with POG or RES to provide a comprehensive understanding of alterations in gene expression and the molecular mechanisms involved. Cultured human fetal osteoblastic hFOB 1.19 cells were treated with the test compounds, and then RNA was used to prepare RNA-seq libraries, that were sequenced using a NovaSeq 6000. Treatment with POG or RES increased osteoblast proliferation and reduced apoptosis. Transcriptomic profiling showed that of the 29,762 genes investigated, 3177 were differentially expressed (1481 upregulated, 1696 downregulated, FDR ≤ 0.05) in POG-treated osteoblasts. In the RES-treated osteoblasts, 2288 genes were differentially expressed (DGEs, 1068 upregulated, 1220 downregulated, FDR ≤ 0.05). Ingenuity® Pathway Analysis (IPA) of DGEs from RES or POG-treated osteoblasts revealed significant downregulation of the apoptosis, osteoarthritis and HIF1α canonical pathways, and a significant reduction in Rankl mRNA expression. The data suggest that RES and POG have both anabolic and anticlastogenic effects.
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Affiliation(s)
- Keila C Ostos Mendoza
- School of Medicine and Health Sciences, Tecnológico de Monterrey, Av. Ignacio Morones Prieto 3000, Sertoma, Monterrey 64710, N.L., Mexico
- Clinical Pharmacognosy Laboratory, Department of Pharmacy Practice, College of Pharmacy, PAHO/WHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Karen D Garay Buenrostro
- School of Medicine and Health Sciences, Tecnológico de Monterrey, Av. Ignacio Morones Prieto 3000, Sertoma, Monterrey 64710, N.L., Mexico
- Clinical Pharmacognosy Laboratory, Department of Pharmacy Practice, College of Pharmacy, PAHO/WHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Pinal N Kanabar
- Research Informatics Core, Research Resources Center, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Mark Maienschein-Cline
- Research Informatics Core, Research Resources Center, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Nina S Los
- Core Genomics Facility, Research Resource Center, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Zarema Arbieva
- Core Genomics Facility, Research Resource Center, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Nishikant A Raut
- Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL 60612, USA
- Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033, India
| | - Temitope O Lawal
- Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL 60612, USA
- Department of Pharmaceutical Microbiology, University of Ibadan, Ibadan 200132, Nigeria
| | - Alice M López
- Clinical Pharmacognosy Laboratory, Department of Pharmacy Practice, College of Pharmacy, PAHO/WHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
- Department of Chemistry and Nanotechnology, Tecnológico de Monterrey, Ave Eugenio Garza Sada 2501, Monterrey 64710, N.L., Mexico
| | - Paulina Cabada-Aguirre
- Clinical Pharmacognosy Laboratory, Department of Pharmacy Practice, College of Pharmacy, PAHO/WHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
- Department of Chemistry and Nanotechnology, Tecnológico de Monterrey, Ave Eugenio Garza Sada 2501, Monterrey 64710, N.L., Mexico
| | - Diego A Luna-Vital
- Institute for Obesity Research, Tecnologico de Monterrey, Monterrey 64710, N.L., Mexico
| | - Gail B Mahady
- Clinical Pharmacognosy Laboratory, Department of Pharmacy Practice, College of Pharmacy, PAHO/WHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
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16
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Lin L, Guo Z, He E, Long X, Wang D, Zhang Y, Guo W, Wei Q, He W, Wu W, Li J, Wo L, Hong D, Zheng J, He M, Zhao Q. SIRT2 regulates extracellular vesicle-mediated liver-bone communication. Nat Metab 2023; 5:821-841. [PMID: 37188819 PMCID: PMC10229428 DOI: 10.1038/s42255-023-00803-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 04/11/2023] [Indexed: 05/17/2023]
Abstract
The interplay between liver and bone metabolism remains largely uncharacterized. Here, we uncover a mechanism of liver-bone crosstalk regulated by hepatocyte SIRT2. We demonstrate that hepatocyte SIRT2 expression is increased in aged mice and elderly humans. Liver-specific SIRT2 deficiency inhibits osteoclastogenesis and alleviates bone loss in mouse models of osteoporosis. We identify leucine-rich α-2-glycoprotein 1 (LRG1) as a functional cargo in hepatocyte-derived small extracellular vesicles (sEVs). In SIRT2-deficient hepatocytes, LRG1 levels in sEVs are upregulated, leading to increased transfer of LRG1 to bone-marrow-derived monocytes (BMDMs), and in turn, to inhibition of osteoclast differentiation via reduced nuclear translocation of NF-κB p65. Treatment with sEVs carrying high levels of LRG1 inhibits osteoclast differentiation in human BMDMs and in mice with osteoporosis, resulting in attenuated bone loss in mice. Furthermore, the plasma level of sEVs carrying LRG1 is positively correlated with bone mineral density in humans. Thus, drugs targeting hepatocyte-osteoclast communication may constitute a promising therapeutic strategy for primary osteoporosis.
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Affiliation(s)
- Longshuai Lin
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Zengya Guo
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Enjun He
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xidai Long
- Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Difei Wang
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yingting Zhang
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weihong Guo
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qian Wei
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei He
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wanying Wu
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingchi Li
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lulu Wo
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dengli Hong
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Junke Zheng
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ming He
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
| | - Qinghua Zhao
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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17
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Abdollahi S, Vajdi M, Meshkini F, Vasmehjani AA, Sangsefidi ZS, Clark CC, Soltani S. Resveratrol may mildly improve renal function in the general adult population: A systematic review and meta-analysis of randomized controlled clinical trials. Nutr Res 2023; 113:1-13. [PMID: 36996691 DOI: 10.1016/j.nutres.2023.03.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 03/06/2023] [Accepted: 03/06/2023] [Indexed: 03/30/2023]
Abstract
Whether renal health biomarkers can benefit from resveratrol supplements is unknown. Thus, we conducted a systematic review and meta-analysis to summarize evidence from randomized controlled trials investigating the effect of resveratrol supplementation on renal health biomarkers. We hypothesized that resveratrol supplementation is associated with improved renal health biomarkers. Four electronic databases, including PubMed, Scopus, and Institute for Scientific Information Web of Science, and Cochrane Central, were searched for relevant articles up to February 2023. The pooled effect sizes were estimated using a random effects model and expressed as weighted mean difference (WMD) and 95% CI. In total, 32 articles were eligible for inclusion in the current meta-analysis. The pooled results indicated that resveratrol significantly decreased blood urea nitrogen (weighted mean difference [WMD]= -0.84 mg/dL; 95% CI, -1.48 to -0.20; P = .01; I2 = 64.4%) and creatinine levels (WMD = -1.90 µmol/L; 95% CI, -3.59 to -0.21; P = .03; I2= 52.1%), and increased glomerular filtration rate (WMD = 7.58 mL/min/1.73 m2; 95% CI, 5.25-9.91; P < .001; I2 = 0%). The favorable change of blood urea nitrogen was significant in studies with short follow-up duration (12 weeks or less), with lower doses of resveratrol (less than 500 mg/d), and those conducted in patients with diabetes. However, higher doses of resveratrol are needed to observe significant reductions in creatinine. No significant change was observed in albumin, total protein, and uric acid concentrations. This meta-analysis provides a low certainty of evidence indicating a mild renal protective effect of resveratrol in adults. Further high-quality evidence in patients with impaired renal function and estimates of mortality risk in these patients is required before resveratrol can be advocated as an adjuvant therapy.
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18
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The Impact of Plasma Membrane Ion Channels on Bone Remodeling in Response to Mechanical Stress, Oxidative Imbalance, and Acidosis. Antioxidants (Basel) 2023; 12:antiox12030689. [PMID: 36978936 PMCID: PMC10045377 DOI: 10.3390/antiox12030689] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/01/2023] [Accepted: 03/03/2023] [Indexed: 03/14/2023] Open
Abstract
The extracellular milieu is a rich source of different stimuli and stressors. Some of them depend on the chemical–physical features of the matrix, while others may come from the ‘outer’ environment, as in the case of mechanical loading applied on the bones. In addition to these forces, a plethora of chemical signals drives cell physiology and fate, possibly leading to dysfunctions when the homeostasis is disrupted. This variety of stimuli triggers different responses among the tissues: bones represent a particular milieu in which a fragile balance between mechanical and metabolic demands should be tuned and maintained by the concerted activity of cell biomolecules located at the interface between external and internal environments. Plasma membrane ion channels can be viewed as multifunctional protein machines that act as rapid and selective dual-nature hubs, sensors, and transducers. Here we focus on some multisensory ion channels (belonging to Piezo, TRP, ASIC/EnaC, P2XR, Connexin, and Pannexin families) actually or potentially playing a significant role in bone adaptation to three main stressors, mechanical forces, oxidative stress, and acidosis, through their effects on bone cells including mesenchymal stem cells, osteoblasts, osteoclasts, and osteocytes. Ion channel-mediated bone remodeling occurs in physiological processes, aging, and human diseases such as osteoporosis, cancer, and traumatic events.
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19
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Soltani S, Sharifi-Zahabi E, Sangsefidi ZS, Ahmadi Vasmehjani A, Meshkini F, Clayton ZS, Abdollahi S. The effect of resveratrol supplementation on biomarkers of liver health: A systematic review and meta-analysis of randomized controlled trials. Phytother Res 2023; 37:1153-1166. [PMID: 36642444 DOI: 10.1002/ptr.7719] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 10/25/2022] [Accepted: 12/18/2022] [Indexed: 01/17/2023]
Abstract
This study aimed to evaluate the effect of resveratrol on liver biomarkers in adult participants, using systematic review and meta-analysis of randomized controlled trials. PubMed, Scopus, Web of Science and Cochran Library was searched, up to October 2021. The pooled effects were calculated using a random-effects model and expressed as weighted mean difference and 95% confidence interval. The methodological quality of studies as well as certainty of evidence were assessed by standard tools. Thirty-seven relevant trials were found. Although overall analysis found no significant change, subgroup analysis showed a significant improvement in alanine aminotransferase (ALT; -7.79 U/L) and glutamyl transferase (-6.0 U/L) in patients with liver disorders, and ALT (-2.22 U/L) in younger adults; however, high-dose supplementation (>1,000 mg/day) appeared to increase alkaline phosphatase concentration (+5.07 U/L). ALT also increased in older adults (+2.33 U/L) following resveratrol supplementation. We found resveratrol did not have a significant effect on liver health in the general population. However, resveratrol could be effective in patients with liver disorders. Our findings also suggest that high-dose resveratrol administration and supplementation in older adults should be performed with caution. Further high-quality clinical trials are also needed to firmly establish the clinical efficacy of resveratrol.
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Affiliation(s)
- Sepideh Soltani
- Yazd Cardiovascular Research Center, Non-Communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Elham Sharifi-Zahabi
- School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zohreh Sadat Sangsefidi
- Department of Nutrition, School of Public Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Azam Ahmadi Vasmehjani
- Department of Nutrition, School of Public Health, Shahid Sadughi University of Medical Sciences, Yazd, Iran
| | - Fatemeh Meshkini
- Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zachary Stephen Clayton
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, USA
| | - Shima Abdollahi
- Department of Nutrition, School of Public Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
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20
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Lorusso F, Scarano A, Fulle S, Valbonetti L, Mancinelli R, Di Filippo ES. Effectiveness of Apigenin, Resveratrol, and Curcumin as Adjuvant Nutraceuticals for Calvarial Bone Defect Healing: An In Vitro and Histological Study on Rats. Nutrients 2023; 15:nu15051235. [PMID: 36904236 PMCID: PMC10005597 DOI: 10.3390/nu15051235] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 02/24/2023] [Accepted: 02/27/2023] [Indexed: 03/05/2023] Open
Abstract
Bone healing is a major clinical issue, especially in bone defects of critical dimensions. Some studies have reported in vivo positive effects on bone healing by some bioactive compounds, such as the phenolic derivatives found in vegetables and plants, such as resveratrol, curcumin, and apigenin. The aim of this work was (1) to analyze in vitro in human dental pulp stem cells the effects of these three natural compounds on the gene expression of related genes downstream to RUNX2 and SMAD5, key factor transcriptions associated with osteoblast differentiation, in order to better understand the positive effects that can occur in vivo in bone healing, and (2) to evaluate in vivo the effects on bone healing of critical-size defects in the calvaria in rats of these three nutraceuticals tested in parallel and for the first time administered by the gastric route. Upregulation of the RUNX2, SMAD5, COLL1, COLL4, and COLL5 genes in the presence of apigenin, curcumin, and resveratrol was detected. In vivo, apigenin induced more consistent significant bone healing in critical-size defects in rat calvaria compared to the other study groups. The study findings encourage a possible therapeutic supplementation with nutraceuticals during the bone regeneration process.
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Affiliation(s)
- Felice Lorusso
- Department of Innovative Technologies in Medicine & Dentistry, University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
- Correspondence: (F.L.); (R.M.)
| | - Antonio Scarano
- Department of Innovative Technologies in Medicine & Dentistry, University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
| | - Stefania Fulle
- Department of Neuroscience, Imaging and Clinical Sciences, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Luca Valbonetti
- Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy
| | - Rosa Mancinelli
- Department of Neuroscience, Imaging and Clinical Sciences, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Correspondence: (F.L.); (R.M.)
| | - Ester Sara Di Filippo
- Department of Neuroscience, Imaging and Clinical Sciences, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
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21
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Marcucci G, Domazetovic V, Nediani C, Ruzzolini J, Favre C, Brandi ML. Oxidative Stress and Natural Antioxidants in Osteoporosis: Novel Preventive and Therapeutic Approaches. Antioxidants (Basel) 2023; 12:antiox12020373. [PMID: 36829932 PMCID: PMC9952369 DOI: 10.3390/antiox12020373] [Citation(s) in RCA: 63] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/27/2023] [Accepted: 01/30/2023] [Indexed: 02/09/2023] Open
Abstract
This review reports in detail the cellular and molecular mechanisms which regulate the bone remodeling process in relation to oxidative stress (OS), inflammatory factors, and estrogen deficiency. OS is considered an important pathogenic factor of osteoporosis, inducing osteocyte apoptosis and varying levels of specific factors, such as receptor activator κB ligand (RANKL), sclerostin, and, according to recent evidence, fibroblast growth factor 23, with consequent impairment of bone remodeling and high bone resorption. Bone loss increases the risk of fragility fractures, and the most commonly used treatments are antiresorptive drugs, followed by anabolic drugs or those with a double effect. In addition, recent data show that natural antioxidants contained in the diet are efficient in preventing and reducing the negative effects of OS on bone remodeling and osteocytes through the involvement of sirtuin type 1 enzyme. Indeed, osteocytes and some of their molecular factors are considered potential biological targets on which antioxidants can act to prevent and reduce bone loss, as well as to promote bone anabolic and regenerative processes by restoring physiological bone remodeling. Several data suggest including antioxidants in novel therapeutic approaches to develop better management strategies for the prevention and treatment of osteoporosis and OS-related bone diseases. In particular, anthocyanins, as well as resveratrol, lycopene, oleuropein, some vitamins, and thiol antioxidants, could have protective and therapeutic anti-osteoporotic effects.
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Affiliation(s)
- Gemma Marcucci
- Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy
| | - Vladana Domazetovic
- Department of Paediatric Haematology-Oncology, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
| | - Chiara Nediani
- Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy
- Correspondence:
| | - Jessica Ruzzolini
- Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy
| | - Claudio Favre
- Department of Paediatric Haematology-Oncology, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
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22
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Wang X, Lu C, Chen Y, Wang Q, Bao X, Zhang Z, Huang X. Resveratrol promotes bone mass in ovariectomized rats and the SIRT1 rs7896005 SNP is associated with bone mass in women during perimenopause and early postmenopause. Climacteric 2023; 26:25-33. [PMID: 35674253 DOI: 10.1080/13697137.2022.2073809] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVE This study aimed to examine the effects of SIRT1 agonist resveratrol on bone mass in ovariectomized (OVX) rats and the SIRT1 single-nucleotide polymorphism (SNP) rs7896005 on bone mass in women during menopause and early postmenopause. METHODS An animal experiment was conducted on rats that were sham-operated (SHAM), OVX or OVX and different administered doses of resveratrol. Serum markers and femur microstructure and staining were assessed. A cross-sectional study was conducted in women undergoing menopause. SIRT1 protein and SIRT1 SNP rs7896005 were evaluated. RESULTS OVX rats administered resveratrol, especially high doses, showed lower bone loss than OVX rats. Serum osteoprotegerin (OPG) and femur SIRT1, β-catenin and bone mineral density (BMD) were significantly increased, whereas receptor activator of NF-κB ligand (RANKL) was significantly decreased. Serum SIRT1 levels were significantly lower in women with low bone mass (p < 0.01). Women with the CA genotype of rs7896005 had lower bone mass than those with the CC genotype. The A allele showed a significant negative effect on bone loss risk (odds ratio = 3.48; p = 0.025). CONCLUSIONS Resveratrol stimulated SIRT1 expression and Wnt/β-catenin signaling to promote bone mass in rat femurs. Among women in perimenopause and early postmenopause, SIRT1 protected bone mass, and the A allele of SIRT1 rs7896005 was a risk factor for reduced bone mass.
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Affiliation(s)
- X Wang
- Department of Reproduction Center, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, China
| | - C Lu
- Department of Gynecology, The First People's Hospital of Xiaoshan District, Hangzhou, China
| | - Y Chen
- Zhejiang Chinese Medical University, Hangzhou, China
| | - Q Wang
- Nanjing Medical University, Nanjing, China
| | - X Bao
- Zhejiang Chinese Medical University, Hangzhou, China
| | - Z Zhang
- Department of Reproductive Endocrinology Center, Hangzhou Women's Hospital, Hangzhou, China
| | - X Huang
- Department of Reproduction Center, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, China
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23
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Liu ZM, Li SY, Huang Q, Zeng FF, Li BL, Cao WT, Chen YM. Greater habitual resveratrol intakes were associated with lower risk of hip fracture- a 1:1 matched case-control study in Chinese elderly. Phytother Res 2023; 37:672-678. [PMID: 36205605 DOI: 10.1002/ptr.7645] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 08/27/2022] [Accepted: 09/18/2022] [Indexed: 11/07/2022]
Abstract
The aim of the study was to testify the association of dietary resveratrol (RSV) intakes with hip fracture risk in Chinese elderly. This was a 1:1 age- and gender- matched case-control study. Eligible cases were newly diagnosed patients of hip fracture. Dietary assessment was made by a 79-item validated food frequency questionnaire. Habitual RSV intakes were estimated as the sum of trans- and cis- isomers of resveratrol and piceid according to the available database. Multivariable conditional logistic regression was applied to examine the relationship of dietary RSV and RSV-rich foods with hip fracture risk. A total of 1,070 pairs of hip fracture incident cases and controls were recruited and 1,065 were included for analysis. Compared with the lowest group, total RSV in the highest quartile group had significantly reduced hip fracture risk by 66.3% (OR: 0.337, 0.222 ~ 0.571, ptrend < 0.001). Similar findings were observed for cis- and trans-RSV, cis- and trans-Piceid, as well as RSV-rich foods (grapes, apples and nuts) respectively. Subgroup analysis suggested more evident findings among female and less obese participants. Our findings demonstrated that higher habitual RSV intakes and RSV-rich foods, even in a relatively low amount, were associated with reduced risk of hip fracture in Chinese elderly.
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Affiliation(s)
- Zhao-Min Liu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Shu-Yi Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Qi Huang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Fang-Fang Zeng
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Bao-Lin Li
- Guangzhou Orthopaedics Trauma Hospital, Guangzhou, China
| | - Wen-Ting Cao
- Department of Epidemiology, School of Public Health, Hainan Medical University, Haikou, China
| | - Yu-Ming Chen
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
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Venkat R, Verma E, Daimary UD, Kumar A, Girisa S, Dutta U, Ahn KS, Kunnumakkara AB. The Journey of Resveratrol from Vineyards to Clinics. Cancer Invest 2023; 41:183-220. [PMID: 35993769 DOI: 10.1080/07357907.2022.2115057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
With rising technological advancements, several factors influence the lifestyle of people and stimulate chronic inflammation that severely affects the human body. Chronic inflammation leads to a broad range of physical and pathophysiological distress. For many years, non-steroidal drugs and corticosteroids were most frequently used in treating inflammation and related ailments. However, long-term usage of these drugs aggravates the conditions of chronic diseases and is presented with morbid side effects, especially in old age. Hence, the quest for safe and less toxic anti-inflammatory compounds of high therapeutic potential with least adverse side effects has shifted researchers' attention to ancient medicinal system. Resveratrol (RSV) - 3,4,5' trihydroxystilbene is one such naturally available polyphenolic stilbene derivative obtained from various plant sources. For over 2000 years, these plants have been used in Asian medicinal system for curing inflammation-associated disorders. There is a wealth of in vitro, in vivo and clinical evidence that shows RSV could induce anti-aging health benefits including, anti-cancer, anti-inflammatory, anti-oxidant, phytoesterogenic, and cardio protective properties. However, the issue of rapid elimination of RSV through the metabolic system and its low bio-availability is of paramount importance which is being studied extensively. Therefore, in this article, we scientifically reviewed the molecular targets, biological activities, beneficial and contradicting effects of RSV as evinced by clinical studies for the prevention and treatment of inflammation-mediated chronic disorders.
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Affiliation(s)
- Ramya Venkat
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
| | - Elika Verma
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
| | - Uzini Devi Daimary
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
| | - Aviral Kumar
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
| | - Sosmitha Girisa
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
| | - Uma Dutta
- Department of Zoology, Cell and Molecular Biology Laboratory, Cotton University, Guwahati, India
| | - Kwang Seok Ahn
- Department of Science in Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Ajaikumar B Kunnumakkara
- Department of Biosciences and Bioengineering, Cancer Biology Laboratory, Indian Institute of Technology (IIT) Guwahati, Guwahati, India
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25
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Song J, Liu T, Zhao J, Wang S, Dang X, Wang W. Causal associations of hand grip strength with bone mineral density and fracture risk: A mendelian randomization study. Front Endocrinol (Lausanne) 2022; 13:1020750. [PMID: 36578964 PMCID: PMC9792153 DOI: 10.3389/fendo.2022.1020750] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 11/29/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Muscle strength has been shown to exert positive effects on bone health. The causal relationship between hand grip strength and osteoporosis is an important public health issue but is not fully revealed. The goal of this study was to investigate whether and to what extent hand grip strength affects bone mineral density (BMD) and fracture risk. METHODS We conducted a state-of-the-art two-sample Mendelian randomization analysis. Genomewide significant (P<5×10-8) single nucleotide polymorphisms associated with hand grip strength were obtained. Summary level data of BMD and fractures at different body sites (lumbar spine, heel, forearm and femoral neck) was obtained from a large-scale osteoporosis database. The inverse variance weighted method was the primary method used for analysis, and the weighted-median, MR-Egger were utilized for sensitivity analyses. RESULTS The results provided strong evidence that hand grip strength trait was causally and positively associated with lumbar spine BMD (β: 0.288, 95% CI: 0.079 to 0.497; P=0.007), while no causal relationship was found between hand grip strength and BMD at heel (β: -0.081, 95% CI: -0.232 to 0.070; P=0.295), forearm (β: 0.-0.101, 95% CI: -0.451 to 0.248; P=0.571) or femoral neck (β: 0.054, 95% CI: -0.171 to 0.278; P=0.639). In addition, no statistically significant effects were observed for hand grip strength on fracture risks (β: -0.004, 95% CI: -0.019 to 0.012; P=0.662). CONCLUSIONS This study showed a positive causal relationship between hand grip strength and lumbar BMD, which is the most common site of osteoporotic fracture, but did not find a causal relationship between hand grip strength and BMD of heel, forearm, or femoral neck. No statistically significant effect of hand grip strength on fracture risk was observed. This study indicates variations in the abilities of hand grip strength trait to causally influence BMD at different skeleton sites. These results should be considered in further studies and public health measures on osteoporosis prevention strategies.
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Affiliation(s)
| | | | | | | | - Xiaoqian Dang
- The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Wei Wang
- The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
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26
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Naude, MTech (Hom) DF. Chronic Sub-Clinical Systemic Metabolic Acidosis - A Review with Implications for Clinical Practice. J Evid Based Integr Med 2022; 27:2515690X221142352. [PMID: 36448194 PMCID: PMC9716591 DOI: 10.1177/2515690x221142352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
When arterial serum pH remains near the lower pH limit of 7.35 for protracted periods of time, a low-grade, sub-clinical form of acidosis results, referred to in this review as chronic, sub-clinical, systemic metabolic acidosis (CSSMA). This narrative review explores the scientific basis for CSSMA, its consequences for health, and potential therapeutic interventions. The major etiology of CSSMA is the shift away from the ancestral, alkaline diet which was rich in fruit and vegetables, toward the contemporary, acidogenic 'Westernized' diet characterized by higher animal protein consumption and lack of base forming minerals. Urine pH is reduced with high dietary acid load and may be a convenient marker of CSSMA. Evidence suggests further that CSSMA negatively influences cortisol levels potentially contributing significantly to the pathophysiology thereof. Both CSSMA and high dietary acid load are associated with the risk and prognosis of various chronic diseases. Clinical trials show that CSSMA can be addressed successfully through alkalizing the diet by increasing fruit and vegetable intake and/or supplementing with alkaline minerals. This review confirms the existence of a significant body of evidence regarding this low-grade form of acidosis as well as evidence to support its diverse negative implications for health, and concludes that CSSMA is a condition warranting further research.
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Affiliation(s)
- David Francis Naude, MTech (Hom)
- Irma Schutte Foundation, Drummond, South Africa,David Francis Naude, Irma Schutte Foundation, 42 Protea Hill Rd, Drummond, KwaZulu Natal, 3626, South Africa. Postal address: P.O Box 8, Hillcrest, KwaZulu Natal, 3650, South Africa.
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27
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Li Y, Li L, Li X, Luo B, Ye Q, Wang H, Yang L, Zhu X, Han L, Zhang R, Tian H, Wang P. A mechanistic review of chinese medicine polyphenols on bone formation and resorption. Front Pharmacol 2022; 13:1017538. [PMID: 36313339 PMCID: PMC9597080 DOI: 10.3389/fphar.2022.1017538] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 10/03/2022] [Indexed: 11/17/2022] Open
Abstract
Bone reconstruction includes a steady state system of bone formation and bone absorption. This tight coupling requires subtle coordination between osteoblasts and osteoclasts. If this balance is broken, it will lead to bone mass loss, bone density reduction, and bone metabolic diseases, such as osteoporosis. Polyphenols in Chinese herbal medicines are active ingredients in plant extracts with high safety and few side effects, and they can play a role in affecting bone formation and bone resorption. Some of these have estrogen-like effects and can better target bone health in postmenopausal women. The purpose of this review is to provide comprehensive information on the mechanisms underlying the relationship between traditional Chinese medicine polyphenols and bone formation or bone resorption.
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Affiliation(s)
- Yan Li
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Lingyu Li
- Cancer Research Institute, Jinan University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Jinan University, Guangzhou, China
- College of Pharmacy, Jinan University, Guangzhou, China
| | - Xiaoyun Li
- College of Pharmacy, Jinan University, Guangzhou, China
| | - Bingjie Luo
- College of Pharmacy, Jinan University, Guangzhou, China
| | - Qianyun Ye
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Haoyu Wang
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Li Yang
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Jinan University, Guangzhou, China
- College of Pharmacy, Jinan University, Guangzhou, China
| | - Xiaofeng Zhu
- College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Jinan University, Guangzhou, China
| | - Li Han
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Jinan University, Guangzhou, China
- First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Ronghua Zhang
- Cancer Research Institute, Jinan University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Jinan University, Guangzhou, China
- College of Pharmacy, Jinan University, Guangzhou, China
- *Correspondence: Ronghua Zhang, ; Huaqin Tian, ; Panpan Wang,
| | - Huaqin Tian
- Foshan Hospital of Traditional Chinese Medicine, Foshan, China
- *Correspondence: Ronghua Zhang, ; Huaqin Tian, ; Panpan Wang,
| | - Panpan Wang
- Cancer Research Institute, Jinan University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Jinan University, Guangzhou, China
- First Affiliated Hospital of Jinan University, Guangzhou, China
- *Correspondence: Ronghua Zhang, ; Huaqin Tian, ; Panpan Wang,
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28
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Resveratrol Synergistically Promotes BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells. Stem Cells Int 2022; 2022:8124085. [PMID: 35923297 PMCID: PMC9343184 DOI: 10.1155/2022/8124085] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/21/2022] [Indexed: 01/03/2023] Open
Abstract
Background. Mesenchymal stem cells (MSCs) differentiate into osteocytes, adipocytes, and chondrocytes. Resveratrol and bone morphogenetic protein 9 (BMP9) are known osteogenic induction factors of MSCs, but the effect of both resveratrol and BMP9 on osteogenesis is unknown. Herein, we explored whether resveratrol cooperates with BMP9 to improve osteogenic induction. Methods. The osteogenic induction of resveratrol and BMP9 on C3H10T1/2 cells was evaluated by detecting the staining and activity of the early osteogenic marker alkaline phosphatase (ALP). In addition, the late osteogenic effect was measured by the mRNA and protein levels of osteogenic markers, such as osteopontin (OPN) and osteocalcin (OCN). To assess the bone formation function of resveratrol plus BMP9 in vivo, we transplanted BMP9-infected C3H10T1/2 cells into nude mice followed by intragastric injection of resveratrol. Western blot (WB) analysis was utilized to elucidate the mechanism of resveratrol plus BMP9. Results. Resveratrol not only enhanced osteogenic induction alone but also improved BMP9-induced ALP at 3, 5, and 7 d postinduction. Both the early osteogenic markers (ALP, Runx2, and SP7) and the late osteogenic markers (OPN and OCN) were significantly increased when resveratrol was combined with BMP9. The fetal limb explant culture further verified these results. The in vivo bone formation experiment, which involved transplanting BMP9-overexpressing C3H10T1/2 cells into nude mice, also confirmed that resveratrol synergistically enhanced the BMP9-induced bone formation function. Resveratrol phosphorylated adenosine monophosphate- (AMP-) activated protein kinase (AMPK) and stimulated autophagy, but these effects were abolished by inhibiting AMPK and Beclin1 using an inhibitor or siRNA. Conclusions. Resveratrol combined with BMP9 significantly improves the osteogenic induction of C3H10T1/2 cells by activating AMPK and autophagy.
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29
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Lin YY, Takemoto JY, Chang CWT, Peng CA. Mesobiliverdin IXα ameliorates osteoporosis via promoting osteogenic differentiation of mesenchymal stem cells. Biochem Biophys Res Commun 2022; 619:56-61. [PMID: 35738065 DOI: 10.1016/j.bbrc.2022.06.042] [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: 05/24/2022] [Revised: 06/10/2022] [Accepted: 06/14/2022] [Indexed: 11/16/2022]
Abstract
Heme oxygenase-1 (HO-1) expression promotes osteogenesis, but the mechanisms remain unclear and therapeutic strategies using it to target bone disorders such as osteoporosis have not progressed. Mesobiliverdin IXα is a naturally occurring bilin analog of HO-1 catalytic product biliverdin IXα. Inclusion of mesobiliverdin IXα in the feed diet of ovariectomized osteoporotic mice was observed to increase femur bone volume, trabecular thickness and osteogenesis serum markers osteoprotegrin and osteocalcin and to decrease bone resorption serum markers cross-linked N-teleopeptide and tartrate-resistant acid phosphatase 5b. Moreover, in vitro exposure of human bone marrow mesenchymal stem cells to mesobiliverdin IXα enhanced osteogenic differentiation efficiency by two-fold over non-exposed controls. Our results imply that mesobiliverdin IXα promotes osteogenesis in ways that reflect the potential therapeutic effects of induced HO-1 expression in alleviating osteoporosis.
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Affiliation(s)
- Yuan-Yu Lin
- Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan
| | - Jon Y Takemoto
- Department of Biology, Utah State University, Logan, UT, United States
| | - Cheng-Wei T Chang
- Department of Chemistry and Biochemistry, Utah State University, Logan, UT, United States
| | - Ching-An Peng
- Department of Chemical and Biological Engineering, University of Idaho, Moscow, ID, United States.
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Storgaard JH, Løkken N, Madsen KL, Voermans NC, Laforêt P, Nadaj-Pakleza A, Tard C, van Hall G, Vissing J, Ørngreen MC. No effect of resveratrol on fatty acid oxidation or exercise capacity in patients with fatty acid oxidation disorders: A randomized clinical cross-over trial. J Inherit Metab Dis 2022; 45:517-528. [PMID: 35066899 DOI: 10.1002/jimd.12479] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 01/19/2022] [Accepted: 01/20/2022] [Indexed: 11/07/2022]
Abstract
The objective was to investigate whether resveratrol (RSV) can improve exercise capacity in patients with fatty acid oxidation (FAO) disorders. The study was a randomized, double-blind, cross-over trial. Nine patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency or carnitine palmitoyl transferase (CPT) II deficiency were randomized to receive either 8 weeks of 1000 mg day-1 RSV or placebo (P) followed by a 4-weeks wash-out period and subsequently 8 weeks of the opposite treatment. Primary outcome measures were heart rate and FAO as measured via stable isotope technique during constant workload exercise. Secondary outcome measures included fat and glucose metabolism; perceived exertion; as well as subjective measures of energy expenditure, fatigue, and daily function. Eight participants completed the trial. Heart rate did not differ at the end of exercise after treatment with RSV vs placebo (P = .063). Rate of oxidation of palmitate at end of exercise was not different with 1.5 ± 0.8 (RSV) vs 1.3 ± 0.6 (P) μmol kg-1 min-1 (P = .109). Secondary outcomes did not change except for increased plasma glycerol and decreased plasma glucose levels at the end of exercise after treatment with RSV vs placebo. A daily dose of 1000 mg resveratrol does not improve exercise capacity or FAO during exercise in patients with CPTII or VLCAD deficiencies.
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Affiliation(s)
- Jesper H Storgaard
- Copenhagen Neuromuscular Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Nicoline Løkken
- Copenhagen Neuromuscular Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Karen L Madsen
- Copenhagen Neuromuscular Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Nicol C Voermans
- Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - Pascal Laforêt
- Nord/Est/Ile de France Neuromuscular Reference Center, FHU PHENIX, INSERM U1179, Neurology Department, Raymond-Poincaré Teaching Hospital, Garches, AP-HP, Paris Saclay University, France
| | - Aleksandra Nadaj-Pakleza
- Centre de Référence des Maladies Neuromusculaires Nord / Est / Ile-de-France, Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Céline Tard
- Centre de référence des maladies rares neuromusculaires, Nord Est Ile de France, U1171, Hôpital Salengro, CRU de Lille, Lille, France
| | - Gerrit van Hall
- Clinical Metabolomics Core Facility, Clinical Biochemistry, Righospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - John Vissing
- Copenhagen Neuromuscular Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Mette C Ørngreen
- Copenhagen Neuromuscular Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
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31
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Tozzi R, Masi D, Cipriani F, Contini S, Gangitano E, Spoltore ME, Barchetta I, Basciani S, Watanabe M, Baldini E, Ulisse S, Lubrano C, Gnessi L, Mariani S. Circulating SIRT1 and Sclerostin Correlates with Bone Status in Young Women with Different Degrees of Adiposity. Nutrients 2022; 14:nu14050983. [PMID: 35267956 PMCID: PMC8912833 DOI: 10.3390/nu14050983] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 02/22/2022] [Accepted: 02/23/2022] [Indexed: 11/28/2022] Open
Abstract
Sirtuin1 (SIRT1) and sclerostin play important roles in adipose tissue and bone metabolism. We evaluated the circulating SIRT1 and sclerostin relationship with mass and quality of bone while considering the degree of adiposity. Sixty-six premenopausal women (16 underweight, 25 normal weight and 25 with obesity), aged <50 years, were enrolled. Plasma SIRT1, sclerostin and DXA body composition (total fat mass (FM), abdominal visceral adipose tissue, lean mass, trabecular bone score (TBS) and lumbar spine and femoral neck (FN) bone mineral density (BMD)) were assessed. The patients with obesity showed the lowest SIRT1 and TBS values and the highest sclerostin concentrations; BMD increased with FM and BMI and had an inverse association with SIRT1. Sclerostin was negatively correlated with SIRT1 (ρ = −0.37, p = 0.002). When spine BMD, FN BMD and TBS were standardized for BMI, a positive correlation with SIRT1 and a negative correlation with sclerostin were seen (p < 0.005). In the regression analysis, sclerostin was the best independent, negative predictor for BMD and TBS, while SIRT1 directly predicted TBS (p < 0.05). In conclusion, blood measurement of SIRT1 and sclerostin could represent a snapshot of the bone status that, taking into account the degree of adiposity, may reduce the interference of confounding factors in the interpretation of bone health parameters.
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Affiliation(s)
- Rossella Tozzi
- Department of Molecular Medicine, “Sapienza” University of Rome, 00161 Rome, Italy;
| | - Davide Masi
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, “Sapienza” University of Rome, 00161 Rome, Italy; (D.M.); (F.C.); (S.C.); (E.G.); (M.E.S.); (I.B.); (S.B.); (M.W.); (C.L.); (L.G.)
| | - Fiammetta Cipriani
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, “Sapienza” University of Rome, 00161 Rome, Italy; (D.M.); (F.C.); (S.C.); (E.G.); (M.E.S.); (I.B.); (S.B.); (M.W.); (C.L.); (L.G.)
| | - Savina Contini
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, “Sapienza” University of Rome, 00161 Rome, Italy; (D.M.); (F.C.); (S.C.); (E.G.); (M.E.S.); (I.B.); (S.B.); (M.W.); (C.L.); (L.G.)
| | - Elena Gangitano
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, “Sapienza” University of Rome, 00161 Rome, Italy; (D.M.); (F.C.); (S.C.); (E.G.); (M.E.S.); (I.B.); (S.B.); (M.W.); (C.L.); (L.G.)
| | - Maria Elena Spoltore
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, “Sapienza” University of Rome, 00161 Rome, Italy; (D.M.); (F.C.); (S.C.); (E.G.); (M.E.S.); (I.B.); (S.B.); (M.W.); (C.L.); (L.G.)
| | - Ilaria Barchetta
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, “Sapienza” University of Rome, 00161 Rome, Italy; (D.M.); (F.C.); (S.C.); (E.G.); (M.E.S.); (I.B.); (S.B.); (M.W.); (C.L.); (L.G.)
| | - Sabrina Basciani
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, “Sapienza” University of Rome, 00161 Rome, Italy; (D.M.); (F.C.); (S.C.); (E.G.); (M.E.S.); (I.B.); (S.B.); (M.W.); (C.L.); (L.G.)
| | - Mikiko Watanabe
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, “Sapienza” University of Rome, 00161 Rome, Italy; (D.M.); (F.C.); (S.C.); (E.G.); (M.E.S.); (I.B.); (S.B.); (M.W.); (C.L.); (L.G.)
| | - Enke Baldini
- Department of Surgical Sciences, “Sapienza” University of Rome, 00161 Rome, Italy; (E.B.); (S.U.)
| | - Salvatore Ulisse
- Department of Surgical Sciences, “Sapienza” University of Rome, 00161 Rome, Italy; (E.B.); (S.U.)
| | - Carla Lubrano
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, “Sapienza” University of Rome, 00161 Rome, Italy; (D.M.); (F.C.); (S.C.); (E.G.); (M.E.S.); (I.B.); (S.B.); (M.W.); (C.L.); (L.G.)
| | - Lucio Gnessi
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, “Sapienza” University of Rome, 00161 Rome, Italy; (D.M.); (F.C.); (S.C.); (E.G.); (M.E.S.); (I.B.); (S.B.); (M.W.); (C.L.); (L.G.)
| | - Stefania Mariani
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, “Sapienza” University of Rome, 00161 Rome, Italy; (D.M.); (F.C.); (S.C.); (E.G.); (M.E.S.); (I.B.); (S.B.); (M.W.); (C.L.); (L.G.)
- Correspondence: ; Tel.: +39-06499-70721; Fax: +39-06446-1450
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Starup-Linde J, Ornstrup MJ, Kjær TN, Lykkeboe S, Handberg A, Gregersen S, Harsløf T, Pedersen SB, Vestergaard P, Langdahl BL. Bone Density and Structure in Overweight Men With and Without Diabetes. Front Endocrinol (Lausanne) 2022; 13:837084. [PMID: 35360074 PMCID: PMC8960162 DOI: 10.3389/fendo.2022.837084] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/10/2022] [Indexed: 12/04/2022] Open
Abstract
OBJECTIVE Metabolic syndrome (MetS), type 1 diabetes (T1D), and type 2 diabetes, are associated with an increased risk of fractures; however, the impact of obesity on bone deficits in diabetes is unknown. We aimed to compare markers of bone structure, bone density, and bone turnover in non-diabetic overweight men with MetS and overweight men with T1D or T2D. METHODS AND RESEARCH DESIGN In this cross-sectional study we included participants from two previously described study cohorts consisting of participants with diabetes and participants with MetS. Participants underwent dual-energy X-ray absorptiometry measuring areal bone mineral density (aBMD) at the hip and lumbar spine, High Resolution peripheral Quantitative (HRpQCT) scan of the tibia and radius and measurement of circulating bone turnover markers. We compared groups with unpaired t test and performed multiple linear regression with adjustment for age, body mass index, and smoking. RESULTS We included 33 participants with T1D, 25 participants with T2D, and 34 participants with MetS. Bone turnover markers levels were comparable between T1D and MetS. aBMD at the hip was lower in T1D compared to MetS, also after adjustment. P1NP and Osteocalcin levels were lower among individuals with T2D compared to MetS, whereas aBMD were similar between the groups after multiple adjustments. We observed no difference in volumetric BMD at the tibia or radius between MetS and T1D and T2D, respectively. Participants with T2D had a higher trabecular number and lower trabecular separation compared to individuals with MetS at the tibia, which remained signficant after multiple adjustments. CONCLUSION In conclusion, we observed no clinically important differences in bone density or structure between men with T2D, T1D, or MetS. However, men with T2D displayed lower bone turnover compared to MetS highlighting that T2D per se and not obesity, is associated with low bone turnover.
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Affiliation(s)
- Jakob Starup-Linde
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark
- *Correspondence: Jakob Starup-Linde,
| | - Marie Juul Ornstrup
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Thomas Nordstrøm Kjær
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Simon Lykkeboe
- Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
| | - Aase Handberg
- Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, The Faculty of Medicine, Aalborg University, Aalborg, Denmark
| | - Søren Gregersen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - Torben Harsløf
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Steen Bønløkke Pedersen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - Peter Vestergaard
- Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, The Faculty of Medicine, Aalborg University, Aalborg, Denmark
- Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
| | - Bente Lomholt Langdahl
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
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Vescini F, Chiodini I, Falchetti A, Palermo A, Salcuni AS, Bonadonna S, De Geronimo V, Cesareo R, Giovanelli L, Brigo M, Bertoldo F, Scillitani A, Gennari L. Management of Osteoporosis in Men: A Narrative Review. Int J Mol Sci 2021; 22:ijms222413640. [PMID: 34948434 PMCID: PMC8705761 DOI: 10.3390/ijms222413640] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 12/13/2021] [Accepted: 12/15/2021] [Indexed: 12/12/2022] Open
Abstract
Male osteoporosis is a still largely underdiagnosed pathological condition. As a consequence, bone fragility in men remains undertreated mainly due to the low screening frequency and to controversies in the bone mineral density (BMD) testing standards. Up to the 40% of overall osteoporotic fractures affect men, in spite of the fact that women have a significant higher prevalence of osteoporosis. In addition, in males, hip fractures are associated with increased morbidity and mortality as compared to women. Importantly, male fractures occur about 10 years later in life than women, and, therefore, due to the advanced age, men may have more comorbidities and, consequently, their mortality is about twice the rate in women. Gender differences, which begin during puberty, lead to wider bones in males as compared with females. In men, follicle-stimulating hormones, testosterone, estrogens, and sex hormone-binding levels, together with genetic factors, interact in determining the peak of bone mass, BMD maintenance, and lifetime decrease. As compared with women, men are more frequently affected by secondary osteoporosis. Therefore, in all osteoporotic men, a complete clinical history should be collected and a careful physical examination should be done, in order to find clues of a possible underlying diseases and, ultimately, to guide laboratory testing. Currently, the pharmacological therapy of male osteoporosis includes aminobisphosphonates, denosumab, and teriparatide. Hypogonadal patients may be treated with testosterone replacement therapy. Given that the fractures related to mortality are higher in men than in women, treating male subjects with osteoporosis is of the utmost importance in clinical practice, as it may impact on mortality even more than in women.
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Affiliation(s)
- Fabio Vescini
- Endocrinology and Metabolism Unit, University-Hospital S. Maria della Misericordia, 33100 Udine, Italy; (F.V.); (A.S.S.)
| | - Iacopo Chiodini
- Istituto Auxologico Italiano, IRCCS, 20149 Milan, Italy; (A.F.); (S.B.)
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy;
- Correspondence:
| | - Alberto Falchetti
- Istituto Auxologico Italiano, IRCCS, 20149 Milan, Italy; (A.F.); (S.B.)
| | - Andrea Palermo
- Unit of Endocrinology and Diabetes, Campus Bio-Medico University, 00128 Rome, Italy;
| | - Antonio Stefano Salcuni
- Endocrinology and Metabolism Unit, University-Hospital S. Maria della Misericordia, 33100 Udine, Italy; (F.V.); (A.S.S.)
| | - Stefania Bonadonna
- Istituto Auxologico Italiano, IRCCS, 20149 Milan, Italy; (A.F.); (S.B.)
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy;
| | | | - Roberto Cesareo
- Center of Metabolic Disease, S.M. Goretti Hospital, 04100 Latina, Italy;
| | - Luca Giovanelli
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy;
| | - Martina Brigo
- Department of Medicine, University of Verona, 37129 Verona, Italy; (M.B.); (F.B.)
| | - Francesco Bertoldo
- Department of Medicine, University of Verona, 37129 Verona, Italy; (M.B.); (F.B.)
| | - Alfredo Scillitani
- Unit of Endocrinology, Ospedale “Casa Sollievo della Sofferenza”, IRCCS, San Giovanni Rotondo, 71013 Foggia, Italy;
| | - Luigi Gennari
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy;
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Zhou X, Yuan W, Xiong X, Zhang Z, Liu J, Zheng Y, Wang J, Liu J. HO-1 in Bone Biology: Potential Therapeutic Strategies for Osteoporosis. Front Cell Dev Biol 2021; 9:791585. [PMID: 34917622 PMCID: PMC8669958 DOI: 10.3389/fcell.2021.791585] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 11/12/2021] [Indexed: 02/05/2023] Open
Abstract
Osteoporosis is a prevalent bone disorder characterized by bone mass reduction and deterioration of bone microarchitecture leading to bone fragility and fracture risk. In recent decades, knowledge regarding the etiological mechanisms emphasizes that inflammation, oxidative stress and senescence of bone cells contribute to the development of osteoporosis. Studies have demonstrated that heme oxygenase 1 (HO-1), an inducible enzyme catalyzing heme degradation, exhibits anti-inflammatory, anti-oxidative stress and anti-apoptosis properties. Emerging evidence has revealed that HO-1 is critical in the maintenance of bone homeostasis, making HO-1 a potential target for osteoporosis treatment. In this Review, we aim to provide an introduction to current knowledge of HO-1 biology and its regulation, focusing specifically on its roles in bone homeostasis and osteoporosis. We also examine the potential of HO-1-based pharmacological therapeutics for osteoporosis and issues faced during clinical translation.
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Affiliation(s)
- Xueman Zhou
- State Key Laboratory of Oral Diseases and National Clinical Research Center for West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Lab for Aging Research, State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Wenxiu Yuan
- State Key Laboratory of Oral Diseases and National Clinical Research Center for West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Lab for Aging Research, State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Xiong
- State Key Laboratory of Oral Diseases and National Clinical Research Center for West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zhenzhen Zhang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Lab for Aging Research, State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Jiaqi Liu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Lab for Aging Research, State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Yingcheng Zheng
- State Key Laboratory of Oral Diseases and National Clinical Research Center for West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Lab for Aging Research, State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Jun Wang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jin Liu
- Lab for Aging Research, State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
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Liu X, Tao J, Yao Y, Yang P, Wang J, Yu M, Hou J, Zhang Y, Gui L. Resveratrol induces proliferation in preosteoblast cell MC3T3-E1 via GATA-1 activating autophagy. Acta Biochim Biophys Sin (Shanghai) 2021; 53:1495-1504. [PMID: 34637502 DOI: 10.1093/abbs/gmab135] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Indexed: 01/08/2023] Open
Abstract
Resveratrol (RSV) could promote osteogenic activity, but its clinical application has been hampered in view of its poor bioavailability. Therefore, it is desirable to identify with certainty the molecular target of its bone mass boosting function, which is crucial to the design of an effective therapeutic strategy for the optimal treatment of osteoporosis. Emerging evidence has indicated that GATA-1, an important transcription factor in megakaryocyte and erythrocyte differentiation, can directly activate autophagy in erythrocytes, alluding to its impact on bone metabolism. In light of this, we sought to determine whether GATA-1 would be a putative target by which RSV would act on osteoblast proliferation and, if so, to explore the underlying mechanism involved in the process. We examined the cell viability, colony formation, cell cyclin expression, autophagy level, and the expression levels of GATA-1 and adenosine 5'-monophosphate (AMP)-activated protein kinase α (AMPKα) in osteoblastic cell strain MC3T3-E1. The results showed that RSV promoted the proliferation process in MC3T3-E1 coupled with increased expression of GATA-1 and phosphorylated AMPKα and activated autophagy. When GATA-1 was interfered with siRNA, both autophagy and proliferation were decreased. Administration of the agonist of phosphorylated AMPKα1 (Thr172) promoted the translocation of GATA-1 into the nucleus. Based on the above results, we concluded that RSV induces the proliferation of MC3T3-E1 by increasing GATA-1 expression, which thence activates autophagy; and of note, AMPKα is one of the upstream regulators of GATA-1.
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Affiliation(s)
- Xiang Liu
- Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, China
| | - Jun Tao
- Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, China
| | - Yueyi Yao
- Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, China
| | - Ping Yang
- Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, China
| | - Juhui Wang
- Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, China
| | - Mali Yu
- Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, China
| | - Jianhong Hou
- Department of Orthopaedics, The Third People’s Hospital of Yunnan Province, Kunming 650101, China
| | - Ying Zhang
- Faculty of Nursing, Kunming Medical University, Kunming 650500, China
| | - Li Gui
- Department of Endocrinology, The Third People’s Hospital of Yunnan Province, Kunming 650101, China
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36
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Zeraattalab-Motlagh S, Jayedi A, Shab-Bidar S. The effects of resveratrol supplementation in patients with type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease: an umbrella review of meta-analyses of randomized controlled trials. Am J Clin Nutr 2021; 114:1675-1685. [PMID: 34320173 DOI: 10.1093/ajcn/nqab250] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Accepted: 07/08/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Uncertainty remains about the estimates of the effects for resveratrol supplementation, including the certainty of the evidence for each estimate and the magnitude of the observed impact based on the minimal important difference. OBJECTIVE We aimed to provide an overview of the effects of resveratrol supplementation, in comparison to control groups, for the management of cardiometabolic risk factors in patients with type 2 diabetes (T2D), metabolic syndrome (MetS), and nonalcoholic fatty liver disease (NAFLD). METHODS PubMed, Scopus, and ISI Web of Science were searched from inception to May 2021. For each meta-analysis, the mean difference and its 95% CI were recalculated using a random-effects model. The certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. RESULTS We identified 11 meta-analyses corresponding to 29 outcomes in 1476 individuals with T2D, 17 meta-analyses reporting 26 outcomes in 727 participants with the MetS, and 10 meta-analyses reporting 24 outcomes in 271 patients with NAFLD. Resveratrol supplementation had beneficial effects on some outcomes such as blood pressure, lipid profile, glycemic control, and insulin resistance in T2D, waist circumference in MetS, and body-weight and inflammation markers in NAFLD; however, for almost all outcomes, the magnitude of the effect was trivial, the certainty of evidence was very low to low, or the number of trials was too few. In the case of glycated hemoglobin (HbA1c), there was evidence that resveratrol can exert favorable and clinically important effects in the short term (<12 wk; mean difference: -1.05%, 95% CI: -2.09%, -0.02%; n = 6; GRADE = moderate). CONCLUSIONS Current evidence does not support supplementation with resveratrol for the management of cardiometabolic risk factors in patients with T2D, MetS, and NAFLD. In the case of HbA1c, subject to the limitations such as short-term follow-up and small sample size, there was a clinically important effect. The protocol of the present systematic review was registered in Open Science Framework (https://osf.io/ake85; registration doi: 10.17605/OSF.IO/AKE85).
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Affiliation(s)
- Sheida Zeraattalab-Motlagh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Ahmad Jayedi
- Food Safety Research Center (Salt), Semnan University of Medical Sciences, Semnan, Iran
| | - Sakineh Shab-Bidar
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
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37
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Ren Z, Raut NA, Lawal TO, Patel SR, Lee SM, Mahady GB. Peonidin-3-O-glucoside and cyanidin increase osteoblast differentiation and reduce RANKL-induced bone resorption in transgenic medaka. Phytother Res 2021; 35:6255-6269. [PMID: 34704297 DOI: 10.1002/ptr.7271] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 12/23/2020] [Accepted: 01/23/2021] [Indexed: 11/07/2022]
Abstract
Experimental and clinical studies suggest a positive impact of anthocyanins on bone health; however, the mechanisms of anthocyanins altering the differentiation and function of osteoblasts and osteoclasts are not fully understood. This work demonstrates that dietary anthocyanins and resveratrol increased proliferation of cultured human hFOB 1.19 osteoblasts. In addition, treatment of serum starvation of hFOB osteoblasts with anthocyanins and resveratrol at 1.0 μg/ml reduced apoptosis, the Bax/Bcl-2 ratio, p53, and HDAC1 expression, but increased SIRT1/3 and PGC1α mRNA expression, suggesting mitochondrial and epigenetic regulation. In Sp7/osterix:mCherry transgenic medaka, peonidin-3-O-glucoside and resveratrol increased osteoblast differentiation and increased the expression of Sp7/osterix. Cyanidin, peonidin-3-O-glucoside, and resveratrol also reduced RANKL-induced ectopic osteoclast formation and bone resorption in col10α1:nlGFP/rankl:HSE:CFP medaka in doses of 1-4 μg/ml. The results indicate that both cyanidin and peonidin-3-O-glucoside have anabolic effects on bone, increasing osteoblast proliferation and differentiation, mitochondrial biogenesis, and by altering the osteoblast epigenome. Cyanidin and peonidin-3-O-glucoside also reduced RANKL-induced bone resorption in a transgenic medaka model of bone resorption. Thus, peonidin-3-O-glucoside and cyanidin appear to both increase bone formation and reduce bone loss, suggesting that they be further investigated as potential treatments for osteoporosis and osteomalacia.
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Affiliation(s)
- Zhitao Ren
- Department of Pharmacy Practice, College of Pharmacy, WHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.,State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Nishikant A Raut
- Raman Fellow, Department of Pharmacy Practice, College of Pharmacy, WHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.,Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, India
| | - Temitope O Lawal
- Schlumberger Fellow, Department of Pharmacy Practice, College of Pharmacy, WHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.,Department of Pharmaceutical Microbiology, University of Ibadan, Ibadan, Nigeria
| | - Shital R Patel
- Department of Pharmacy Practice, College of Pharmacy, WHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Simon M Lee
- State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Gail B Mahady
- Department of Pharmacy Practice, College of Pharmacy, WHO Collaborating Centre for Traditional Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
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Effects of Extracellular Osteoanabolic Agents on the Endogenous Response of Osteoblastic Cells. Cells 2021; 10:cells10092383. [PMID: 34572032 PMCID: PMC8471159 DOI: 10.3390/cells10092383] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/31/2021] [Accepted: 09/07/2021] [Indexed: 12/27/2022] Open
Abstract
The complex multidimensional skeletal organization can adapt its structure in accordance with external contexts, demonstrating excellent self-renewal capacity. Thus, optimal extracellular environmental properties are critical for bone regeneration and inextricably linked to the mechanical and biological states of bone. It is interesting to note that the microstructure of bone depends not only on genetic determinants (which control the bone remodeling loop through autocrine and paracrine signals) but also, more importantly, on the continuous response of cells to external mechanical cues. In particular, bone cells sense mechanical signals such as shear, tensile, loading and vibration, and once activated, they react by regulating bone anabolism. Although several specific surrounding conditions needed for osteoblast cells to specifically augment bone formation have been empirically discovered, most of the underlying biomechanical cellular processes underneath remain largely unknown. Nevertheless, exogenous stimuli of endogenous osteogenesis can be applied to promote the mineral apposition rate, bone formation, bone mass and bone strength, as well as expediting fracture repair and bone regeneration. The following review summarizes the latest studies related to the proliferation and differentiation of osteoblastic cells, enhanced by mechanical forces or supplemental signaling factors (such as trace metals, nutraceuticals, vitamins and exosomes), providing a thorough overview of the exogenous osteogenic agents which can be exploited to modulate and influence the mechanically induced anabolism of bone. Furthermore, this review aims to discuss the emerging role of extracellular stimuli in skeletal metabolism as well as their potential roles and provide new perspectives for the treatment of bone disorders.
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Li Q, Yang G, Xu H, Tang S, Lee WYW. Effects of resveratrol supplementation on bone quality: a systematic review and meta-analysis of randomized controlled trials. BMC Complement Med Ther 2021; 21:214. [PMID: 34420523 PMCID: PMC8380387 DOI: 10.1186/s12906-021-03381-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 07/20/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The results from clinical trials have revealed that the effects of resveratrol supplementation on bone mineral density (BMD) and bone biomarkers are inconsistent. Our objective was to determine the effects of resveratrol supplementation on BMD and serum bone biomarkers. METHODS PubMed, Cochrane library, EMBASE, Web of science and Scopus were searched up to August 24, 2020. Two reviewers independently performed the articles search and screen according to defined selection criteria. The study quality of the randomized controlled trials (RCTs) was evaluated with the Cochrane scoring system. Heterogeneity among studies was examined by Cochrane Q test. Retrieved data were pooled after mean differences (MD) were computed between two groups for BMD and serum biomarkers. Subgroup analyses were performed to evaluate a potential difference in terms of dose of resveratrol and intervention duration. Sensitivity analysis was executed by omitting studies with imputed values in order to evaluate the influence of these studies on the overall results. RESULTS Ten eligible studies involving 698 subjects were included in this meta-analysis with 401 participants receiving resveratrol and 297 receiving placebo. Supplementation of resveratrol had no statistically significant effects on areal bone mineral density (aBMD) at lumbar spine (MD: -0.02, 95% CI: - 0.05, 0.01, p = 0.26, I2 = 6%), total hip BMD (MD: -0.01, 95% CI: - 0.04, 0.02, p = 0.65, I2 = 0%), and whole body BMD (MD: 0.00, 95% CI: - 0.02, 0.02, p = 0.74, I2 = 0%). Supplementation of resveratrol also did not result in significant change in bone serum markers, including serum alkaline phosphatase (ALP), bone alkaline phosphatase (BAP), osteocalcin (OCN), procollagen I N-terminal propeptide (PINP), C-terminal telopeptide of type I collagen (CTX) and parathyroid hormone (PTH). Subgroup analysis showed the effect of resveratrol supplementation on BMD and serum bone markers were similar in trails of different doses, intervention duration, and pathological conditions of the participants. CONCLUSION Resveratrol supplementation did not show any significant effect on BMD or serum bone markers with the current evidence. Further investigation with more well-organized multicentre randomized trial is warranted.
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Affiliation(s)
- Qiangqiang Li
- State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.,SH Ho Scoliosis Research Laboratory, Joint Scoliosis Research Centre of the Chinese University of Hong Kong and Nanjing University, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.,Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Guangpu Yang
- SH Ho Scoliosis Research Laboratory, Joint Scoliosis Research Centre of the Chinese University of Hong Kong and Nanjing University, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.,Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Hongtao Xu
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Shaowen Tang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
| | - Wayne Yuk-Wai Lee
- SH Ho Scoliosis Research Laboratory, Joint Scoliosis Research Centre of the Chinese University of Hong Kong and Nanjing University, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. .,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. .,Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
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Austermann K, Baecker N, Zwart SR, Fimmers R, Frippiat JP, Stehle P, Smith SM, Heer M. Antioxidant Supplementation Does Not Affect Bone Turnover Markers During 60 Days of 6° Head-Down Tilt Bed Rest: Results from an Exploratory Randomized Controlled Trial. J Nutr 2021; 151:1527-1538. [PMID: 33831949 DOI: 10.1093/jn/nxab036] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 11/02/2020] [Accepted: 01/29/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Immobilization and related oxidative stress are associated with bone loss. Antioxidants like polyphenols, omega-3 fatty acids, vitamins, and micronutrients may mitigate these negative effects on bone metabolism through scavenging of free radicals. OBJECTIVES We hypothesized that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR) would reduce bone resorption and increase bone formation compared to nonsupplemented controls. METHODS This exploratory randomized, controlled, single-blind intervention study conducted in a parallel design included 20 healthy male volunteers (age, 34 ± 8 years; weight, 74 ± 6 kg). The study consisted of a 14-day adaptation phase [baseline data collection (BDC)], followed by 60 days of HDBR and a 14-day recovery period (R). In the antioxidant group, volunteers received an antioxidant cocktail (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E, and 80 μg/d selenium) with their daily meals. In the control group, volunteers received no supplement. Based on their body weight, all volunteers received an individually tailored and strictly controlled diet, consistent with DRIs. We analyzed biomarkers of calcium homeostasis, bone formation, and bone resorption during BDC, HDBR, and R, as well as for 30 days after the end of HDBR. Data were analyzed by linear mixed models. RESULTS The antioxidant supplement did not affect serum calcium, parathyroid hormone, urinary C-telopeptide of type I collagen (CTX), urinary N-telopeptide of type I collagen, serum β-C-telopeptide of type I collagen (β-CTX), bone alkaline phosphatase, aminoterminal propeptide of type I collagen, osteocalcin, or urinary calcium excretion. In both groups, typical bed rest-related changes were observed. CONCLUSIONS Supplementation of an antioxidant cocktail to a diet matching the DRIs did not affect bone resorption or formation during 60 days of HDBR in healthy young men. This trial was registered at clinicaltrials.gov as NCT03594799.
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Affiliation(s)
- Katharina Austermann
- Nutritional Physiology, Institute of Nutritional and Food Sciences, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
| | - Natalie Baecker
- IUBH International University of Applied Sciences, Bad Reichenhall, Germany
| | - Sara R Zwart
- Department of Preventive Medicine and Community Health, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Rolf Fimmers
- Department of Medical Biometry, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
| | - Jean-Pol Frippiat
- Stress, Immunity, Pathogens Laboratory, Lorraine University, Nancy, France
| | - Peter Stehle
- Nutritional Physiology, Institute of Nutritional and Food Sciences, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
| | - Scott M Smith
- Human Health and Performance Directorate, National Aeronautics and Space Administration Johnson Space Center, Houston, TX, USA
| | - Martina Heer
- Nutritional Physiology, Institute of Nutritional and Food Sciences, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.,IUBH International University of Applied Sciences, Bad Reichenhall, Germany
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Cai H, Scott EN, Britton RG, Parrott E, Ognibene TJ, Malfatti M, Khan M, Steward WP, Brown K. Distribution and metabolism of [14C]-resveratrol in human prostate tissue after oral administration of a "dietary-achievable" or "pharmacological" dose: what are the implications for anticancer activity? Am J Clin Nutr 2021; 113:1115-1125. [PMID: 33675348 PMCID: PMC8106746 DOI: 10.1093/ajcn/nqaa414] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 12/08/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The dietary polyphenol resveratrol prevents various malignancies in preclinical models, including prostate cancer. Despite attempts to translate findings to humans, gaps remain in understanding pharmacokinetic-pharmacodynamic relations and how tissue concentrations affect efficacy. Such information is necessary for dose selection and is particularly important given the low bioavailability of resveratrol. OBJECTIVES This study aimed to determine concentrations of resveratrol in prostate tissue of men after a dietary-achievable (5 mg) or pharmacological (1 g) dose. We then examined whether clinically relevant concentrations of resveratrol/its metabolites had direct anticancer activity in prostate cell lines. METHODS A window trial was performed in which patients were allocated to 5 mg or 1 g resveratrol daily, or no intervention, before prostate biopsy. Patients (10/group) ingested resveratrol capsules for 7-14 d before biopsy, with the last dose [14C]-labeled, allowing detection of resveratrol species in prostate tissue using accelerator MS. Cellular uptake and antiproliferative properties of resveratrol/metabolites were assessed in cancer and nonmalignant cell cultures using HPLC with UV detection and cell counting, respectively. RESULTS [14C]-Resveratrol species were detectable in prostate tissue of all patients analyzed, with mean ± SD concentrations of 0.08 ± 0.04 compared with 22.1 ± 8.2 pmol/mg tissue for the 5 mg and the 1 g dose, respectively. However, total [14C]-resveratrol equivalents in prostate were lower than we previously reported in plasma and colorectum after identical doses. Furthermore, resveratrol was undetectable in prostate tissue; instead, sulfate and glucuronide metabolites dominated. Although resveratrol reduced prostate cell numbers in vitro over 7 d, the concentrations required (≥10 µM) exceeded the plasma maximum concentration. Resveratrol mono-sulfates and glucuronides failed to consistently inhibit cell growth, partly due to poor cellular uptake. CONCLUSIONS Low tissue concentrations of resveratrol species, coupled with weak antiproliferative activity of its conjugates, suggest daily doses of ≤1 g may not have direct effects on human prostate.This trial was registered at clinicaltrialsregister.eu as EudraCT 2007-002131-91.
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Affiliation(s)
- Hong Cai
- Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom
| | - Edwina N Scott
- Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom
| | - Robert G Britton
- Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom
| | - Emma Parrott
- Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom
| | - Ted J Ognibene
- Lawrence Livermore National Laboratory, Livermore, CA, USA
| | | | - Masood Khan
- University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
| | - William P Steward
- Leicester Cancer Research Centre, University of Leicester, Leicester, United Kingdom
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Abstract
PURPOSE OF REVIEW Nutrition influences skeletal health throughout the lifespan, from the impact of maternal intakes during development, through the development of peak bone mass, to the rate of bone loss during aging. However, there are limited data available on the effects of nutritional supplements on bone density, let alone fracture risk. This review will assess the current literature, focusing on human studies, and emphasizing nutrients where bone density or fracture data are available. RECENT FINDINGS Calcium and vitamin D supplements, in combination, reduce fracture risk, particularly in populations with low intakes. Extensive recent analyses have supported the safety of these interventions at recommended intakes. There is growing evidence that specific isoflavones may improve bone density although fracture data are lacking. Multiple other nutrient supplements may benefit skeletal health, but data are limited. The effect size of nutrient interventions are relatively small, requiring large sample sizes for trials with bone outcomes, may be difficult to blind, and the impact of supplementation may depend on baseline intake. However, nutrition is the only intervention that can be implemented life long and on a population wide basis. Further investigation is needed into the potential benefits of nutritional supplements to determine in which settings supplements may add benefit in addition to dietary intakes.
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Affiliation(s)
- Laila S Tabatabai
- Division of Endocrinology, Houston Methodist Hospital, Houston, TX, USA
| | - Deborah E Sellmeyer
- Division of Endocrinology, Gerontology, and Metabolism, School of Medicine, Stanford University, 300 Pasteur Drive, Room S025, Palo Alto, Stanford, CA, 94305-5103, USA.
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Li Q, Cheng JC, Jiang Q, Lee WY. Role of sirtuins in bone biology: Potential implications for novel therapeutic strategies for osteoporosis. Aging Cell 2021; 20:e13301. [PMID: 33393735 PMCID: PMC7884050 DOI: 10.1111/acel.13301] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 12/10/2020] [Accepted: 12/16/2020] [Indexed: 12/16/2022] Open
Abstract
The decline in bone mass and bone strength and musculoskeletal problems associated with aging constitute a major challenge for affected individuals and the healthcare system globally. Sirtuins 1-7 (SIRT1-SIRT7) are a family of nicotinamide adenine dinucleotide-dependent deacetylases with remarkable abilities to promote longevity and counteract age-related diseases. Sirtuin knockout and transgenic models have provided novel insights into the function and signaling of these proteins in bone homeostasis. Studies have revealed that sirtuins play a critical role in normal skeletal development and homeostasis through their direct action on bone cells and that their dysregulation might contribute to different bone diseases. Preclinical studies have demonstrated that mice treated with sirtuin agonists show protection against age-related, postmenopausal, and immobilization-induced osteoporosis. These findings suggest that sirtuins could be potential targets for the modulation of the imbalance in bone remodeling and treatment of osteoporosis and other bone disorders. The aim of this review was to provide a comprehensive updated review of the current knowledge on sirtuin biology, focusing specifically on their roles in bone homeostasis and osteoporosis, and potential pharmacological interventions targeting sirtuins for the treatment of osteoporosis.
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Affiliation(s)
- Qiangqiang Li
- SH Ho Scoliosis Research LaboratoryDepartment of Orthopaedics and TraumatologyThe Chinese University of Hong KongHong Kong SARChina
- Joint Scoliosis Research Center of the Chinese University of Hong Kong and Nanjing UniversityThe Chinese University of Hong KongHong Kong SARChina
- Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina
| | - Jack Chun‐yiu Cheng
- SH Ho Scoliosis Research LaboratoryDepartment of Orthopaedics and TraumatologyThe Chinese University of Hong KongHong Kong SARChina
- Joint Scoliosis Research Center of the Chinese University of Hong Kong and Nanjing UniversityThe Chinese University of Hong KongHong Kong SARChina
| | - Qing Jiang
- Department of Sports Medicine and Adult Reconstructive SurgeryDrum Tower Hospital affiliated to Medical School of Nanjing UniversityNanjingChina
| | - Wayne Yuk‐wai Lee
- SH Ho Scoliosis Research LaboratoryDepartment of Orthopaedics and TraumatologyThe Chinese University of Hong KongHong Kong SARChina
- Joint Scoliosis Research Center of the Chinese University of Hong Kong and Nanjing UniversityThe Chinese University of Hong KongHong Kong SARChina
- Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina
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de Nigris F, Ruosi C, Colella G, Napoli C. Epigenetic therapies of osteoporosis. Bone 2021; 142:115680. [PMID: 33031975 DOI: 10.1016/j.bone.2020.115680] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/01/2020] [Accepted: 10/02/2020] [Indexed: 12/29/2022]
Abstract
The study of epigenetics reaches its 50th anniversary, however, its clinical application is gradually coming into the clinical setting. Osteoporosis is one of the major and widely diffused bone diseases. Pathogenic mechanisms at the epigenetic level may interfere with bone remodeling occurring during osteoporosis. Preclinical models were used to understand whether such events may interfere with the disease. Besides, observational clinical trials investigated epigenetic-related biomarkers. This effort leads to some epigenetic-related therapies in clinical trials for the treatment of osteoporosis. Bisphosphonates (BPs), target therapy blocking RANK/RANKL pathway, and anti-sclerostin antibody (SOST) are the main therapeutic approaches. However, future large trials will reveal whether epigenetic therapies of osteoporosis will remain a work in progress or data will become more robust in the real-world management of these frailty patients.
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Affiliation(s)
- Filomena de Nigris
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
| | - Carlo Ruosi
- Department of Public Health, Federico II University, 80132 Naples, Italy
| | - Gianluca Colella
- Department of Public Health, Federico II University, 80132 Naples, Italy
| | - Claudio Napoli
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy; IRCCS SDN, 80134 Naples, Italy
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Briskey D, Rao A. Trans-Resveratrol Oral Bioavailability in Humans Using LipiSperse™ Dispersion Technology. Pharmaceutics 2020; 12:pharmaceutics12121190. [PMID: 33302446 PMCID: PMC7763804 DOI: 10.3390/pharmaceutics12121190] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 11/27/2020] [Accepted: 12/02/2020] [Indexed: 12/12/2022] Open
Abstract
Resveratrol is a naturally produced compound that has been well researched for its potential health benefits. The primary hindrance towards resveratrol’s therapeutic efficacy is its traditionally poor oral bioavailability. LipiSperse® is a novel delivery system designed to increase the dispersion of lipophilic ingredients, like resveratrol, in aqueous environments. This single-dose, double-blind, randomized study compared the pharmacokinetics of a commercially available resveratrol with (Veri-Sperse®) and without (Veri-te) the LipiSperse® delivery complex. Healthy adults randomly received a single dose of either 150 Veri-te, 75 Veri-Sperse®, or 150 mg Veri-Sperse®. Venous blood samples were taken prior to dosing in a fasted state and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 h post supplementation. Plasma trans-resveratrol conjugates were measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS). The area under the curve (AUC) (0–24 h), maximum concentration (Cmax), and time of maximum concentration (Tmax) of plasma conjugates were calculated. The 150 mg dose of Veri-Sperse® had a 2-fold increase in absorption (AUC) and a 3-fold increase in Cmax of trans-resveratrol conjugates compared to 150 mg Veri-te. There was no statistical difference between 75 Veri-Sperse and 150 mg Veri-te for AUC or Cmax of resveratrol conjugates. These findings provide support for the use of LipiSperse® to improve absorption of resveratrol.
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Affiliation(s)
- David Briskey
- School of Human Movement and Nutrition Sciences, University of Queensland, Brisbane, QLD 4067, Australia;
- RDC Clinical, Newstead, Brisbane, QLD 4006, Australia
| | - Amanda Rao
- RDC Clinical, Newstead, Brisbane, QLD 4006, Australia
- Correspondence: ; Tel.: +617-3102-4486
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Wong RH, Thaung Zaw JJ, Xian CJ, Howe PR. Regular Supplementation With Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled Trial. J Bone Miner Res 2020; 35:2121-2131. [PMID: 32564438 PMCID: PMC7689937 DOI: 10.1002/jbmr.4115] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 06/11/2020] [Accepted: 06/14/2020] [Indexed: 11/12/2022]
Abstract
Resveratrol, a naturally occurring polyphenol in red grapes and berries, can act as a phytoestrogen. It has been shown to improve both systemic and cerebral circulatory functions, possibly through activation of endothelial estrogen receptors. in vitro and in vivo studies in rodent models also indicate a bone-protective role for resveratrol, particularly in ovariectomized rat models that mimic postmenopausal osteoporosis caused by estrogen deficiency. Hypothesizing a circulatory benefit of resveratrol in bone tissue, we investigated whether resveratrol supplementation could improve bone health in postmenopausal women. The Resveratrol for Healthy Aging in Women (RESHAW) trial was a 24-month randomized, double-blind, placebo-controlled, two-period crossover intervention conducted to evaluate the effects of resveratrol (75 mg twice daily) on cognition, cerebrovascular function, bone health, cardiometabolic markers, and well-being in postmenopausal women. After 12 months of supplementation with resveratrol versus placebo, there were positive effects on bone density in the lumbar spine (+0.016 ± 0.003 g/cm2 ) and neck of femur (+0.005 ± 0.002 g/cm2 ), which were accompanied by a 7.24% reduction in C-terminal telopeptide type-1 collagen levels, a bone resorption marker, compared with placebo. The increase in bone mineral density in the femoral neck resulted in an improvement in T-score (+0.070 ± 0.018) and a reduction in the 10-year probability of major and hip fracture risk. The magnitude of improvement was higher in women with poor bone health biomarker status. Importantly, the improvement in femoral neck T-score with resveratrol correlated with improvement in perfusion. Our subanalysis also revealed that the bone-protective benefit of resveratrol was greater in participants who supplemented with vitamin D plus calcium. Regular supplementation with 75 mg of resveratrol twice daily has the potential to slow bone loss in the lumbar spine and femoral neck, common fracture sites in postmenopausal women without overt osteoporosis. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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Affiliation(s)
- Rachel Hx Wong
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia.,Institute for Resilient Regions, University of Southern Queensland, Springfield Central, Australia
| | - Jay Jay Thaung Zaw
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia
| | - Cory J Xian
- UniSA Clinical & Health Sciences and Cancer Research Institute, University of South Australia, Adelaide, Australia
| | - Peter Rc Howe
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia.,Institute for Resilient Regions, University of Southern Queensland, Springfield Central, Australia.,UniSA Allied Health & Human Performance, University of South Australia, Adelaide, Australia
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Shi Y, Shu H, Wang X, Zhao H, Lu C, Lu A, He X. Potential Advantages of Bioactive Compounds Extracted From Traditional Chinese Medicine to Inhibit Bone Destructions in Rheumatoid Arthritis. Front Pharmacol 2020; 11:561962. [PMID: 33117162 PMCID: PMC7577042 DOI: 10.3389/fphar.2020.561962] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 09/16/2020] [Indexed: 12/14/2022] Open
Abstract
Bone destruction is an important pathological feature of rheumatoid arthritis (RA), which finally leads to the serious decline of life quality in RA patients. Bone metabolism imbalance is the principal factor of bone destruction in RA, which is manifested by excessive osteoclast-mediated bone resorption and inadequate osteoblast-mediated bone formation. Although current drugs alleviate the process of bone destruction to a certain extent, there are still many deficiencies. Recent studies have shown that traditional Chinese medicine (TCM) could effectively suppress bone destruction of RA. Some bioactive compounds from TCM have shown good effect on inhibiting osteoclast differentiation and promoting osteoblast proliferation. This article reviews the research progress of bioactive compounds exacted from TCM in inhibiting bone destruction of RA, so as to provide references for further clinical and scientific research.
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Affiliation(s)
- Yingjie Shi
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
| | - Haiyang Shu
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.,The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xinyu Wang
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.,College of Medicine, Southwest Jiaotong University, Chengdu, China
| | - Hanxiao Zhao
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.,The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Cheng Lu
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
| | - Aiping Lu
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,School of Chinese Medicine, Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University, Hong Kong, Hong Kong
| | - Xiaojuan He
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
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48
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Tao ZS, Zhou WS, Yang M, Xu H. Resveratrol reverses the negative effect of alcohol on hydroxyapatite-coated implant osseointegration in senile female rats. Z Gerontol Geriatr 2020; 53:538-545. [PMID: 31435788 DOI: 10.1007/s00391-019-01595-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 07/23/2019] [Indexed: 10/26/2022]
Abstract
Previous studies have demonstrated the damaging effect of alcohol (ALH) consumption on bone tissue and bone metabolism. Resveratrol (RES) promotes osteoblast proliferation and inhibits osteoclast proliferation and positively affects bone regeneration; however, reports about effects of RES on osseointegration in aged female rats with ALH consumption are limited. This study was designed to investigate the impact of treatment with RES on osseointegration for aged female rats with ALH consumption. This study included 30 female Sprague-Dawley rats (22 months old), weighing approximately 520 g. All animals were randomly divided into 3 groups of 10: a control group (CON) receiving saline, a group receiving ALH and a group receiving ALH + RES until death after 12 weeks. The results of enhanced osseointegration in senile female rats with RES consumption were evaluated by histology, microcomputerized tomography (micro-CT), gene expression analysis and a biomechanical test. The results of this study indicated that ALH + RES showed stronger effects on the improvement of osseointegration in senile female rats with ALH consumption. The ALH + RES produced stronger effects on bone volume per total volume (BV/TV), mean trabecular thickness (Tb.Th), mean trabecular number (Tb.N) and mean trabecular separation (Tb.Sp), connective tissue density (Conn.D) and maximum push-out force for implants, and regulation of osteogenesis and bone resorption-related gene expression. These results seem to indicate that RES intervention reverses the negative effect of alcohol on hydroxyapatite-coated implant osseointegration in senile female rats with ALH consumption.
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Affiliation(s)
- Zhou-Shan Tao
- Department of Trauma orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, No. 2, Zhe shan Xi Road, 241001, Wuhu, Anhui, China
| | - Wan-Shu Zhou
- Department of Geriatrics, The Second Affiliated Hospital of Wannan Medical College, Yijishan Hospital, No. 10, Rehabilitation Road, 241001, Wuhu, Anhui, China
| | - Min Yang
- Department of Trauma orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, No. 2, Zhe shan Xi Road, 241001, Wuhu, Anhui, China.
| | - Hongguang Xu
- Spine Research Center of Wannan Medical College; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution; Dept of Spine Surgery, Yijishan hospital of Wannan Medical College, No. 2, Zhe shan Xi Road, 241001, Wuhu, Anhui, China.
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E Hassan N, A El-Masry S, S M El-Saeed G, Al-Tohamy M, H Thabet E, Aly MM, Mohsen M, Khalil A. Association Between Visceral Adipose Tissue and Estradiol with Bone Health among Obese Women with Metabolic Syndrome. Pak J Biol Sci 2020; 23:1237-1244. [PMID: 32981256 DOI: 10.3923/pjbs.2020.1237.1244] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND OBJECTIVE Visceral Adipose Tissue (VAT) which is associated with a higher risk of Metabolic Syndrome (MS) shows adverse effects on bone health. Moreover, MS is associated with high concentrations of serum estradiol (E2), which is essential for bone, as it inhibits bone resorption. This study aimed to investigate the impact of visceral fat and serum E2 levels on bone health markers (vitamin D, C-terminal peptide, Ca and BMD) in obese women with and without MS. MATERIALS AND METHODS This cross-sectional study was conducted on 64 obese women, with and without MS. Waist Circumference (WC) was measured in cm. Bone Mineral Density (BMD) was assessed by energy X-ray absorptiometry (DEXA), VAT was evaluated using Body Composition Analyzer "Tanita". Serum E2, C-terminal peptide and vitamin D (Vit. D) were assessed using ELISA technique. Serum calcium (Ca), triglyceride (TG), total cholesterol (Tchol), High Density Lipoproteins (HDL), Low Density Lipoproteins (LDL) and Fasting Blood Sugar (FBS) were also assessed. RESULTS In women with MS, VAT showed significant positive correlations with Body Mass Index (BMI), WC and FBS. Whereas, in women without MS, VAT showed significant positive correlations with BMI, TG, age and significant negative correlation with E2. On the other hand, in women with MS, estradiol (E2) had significant negative correlation with age and significant positive correlations with BMD, BMI, FBS and body weight. While, in obese women without MS, it had significant negative correlations with Ca, VAT, age and systolic blood pressure. CONCLUSION In obese women with MS, increased VAT, higher BMI, older age and low E2 levels have clinical significance and hence, they should be considered when predicting bone health risk.
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50
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Qasem RJ. The estrogenic activity of resveratrol: a comprehensive review of in vitro and in vivo evidence and the potential for endocrine disruption. Crit Rev Toxicol 2020; 50:439-462. [DOI: 10.1080/10408444.2020.1762538] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Rani J. Qasem
- Department of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center (KAIMRC) and King Abdulaziz Medical City, National Guard Health Affairs (NGHA), Riyadh, Saudi Arabia
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