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Duman I, Tanrıverdi G, Öztürk Özener H. Effects of vitamin K2 administration on guided bone regeneration in diabetic rats. J Periodontal Res 2024; 59:993-1004. [PMID: 38742688 DOI: 10.1111/jre.13287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 04/29/2024] [Accepted: 05/01/2024] [Indexed: 05/16/2024]
Abstract
AIM The present study aimed to investigate the histomorphometric and immunohistochemical impacts of vitamin K2 on guided bone regeneration (GBR) in calvarial critical-size defects (CSDs) in diabetic rats. METHODS A total of 30 rats were used in this study, comprising 12 non-diabetic (control) rats and 18 with streptozotocin-nicotinamide-induced experimental Diabetes mellitus (DM). In all rats, two calvarial CSDs were created: one defect was left empty (E), the other was treated with bovine-derived bone graft and collagen-based resorbable membrane (GM). Study groups were as follows: control rats administered saline (n = 6, C-E and C-GM groups) or vitamin K2 (n = 6, CK-E and CK-GM groups) and diabetic rats administered saline (n = 6, DM-E and DM-GM groups) or vitamin K2 (n = 6, DMK-E and DMK-GM groups). After 4 weeks of saline or vitamin K2 administration, the rats were euthanized. Bone defect healing and new bone formation were assessed histomorphometrically, and osteocalcin and osteopontin levels were examined immunohistochemically. RESULTS Percentage of new bone formation was greater in CK-GM vs. CK-E and in DMK-GM vs. DMK-E [d = 3.86 (95% CI = 16.38-28.61), d = 1.86, (95% CI = 10.74-38.58), respectively, p < .05]. Bone defect healing scores were higher in CK-GM vs. CK-E and in DMK-GM vs. DMK-E [d = 2.69 (95% CI = -2.12 to -0.87), d = 3.28 (95% CI = 0.98-1.91), respectively, p < .05]. Osteocalcin expression levels were elevated in CK-GM vs. CK-E, in DMK-GM vs. DMK-E [d = 1.19 (95% CI = 0.08-1.41), d = 1.10 (95% CI = 0.02-1.22), respectively p < .05]. Vitamin K2 enhanced osteocalcin expression levels in DMK-E vs. DM-E [d = 2.78, (95% CI = 0.56-1.53), p < .05] and in DMK-GM vs. DM-GM [d = 2.43, (95% CI = 0.65-2.10), p < .05]. Osteopontin expression was enhanced in defects treated with GM vs. E defects [C-GM vs. C-E, d = 1.56 (95% CI = 0.38-2.01); CK-GM vs. CK-E, d = 1.91 (95% CI = 0.49-1.72); DM-GM vs. DM-E, d = 2.34 (95% CI = -1.12 to -0.50); DMK-GM vs. DMK-E, d = 2.00 (95% CI = 0.58-1.91), p < .05]. CONCLUSION The research findings suggest that administering vitamin K2 in GBR for rats with DM favorably impacts bone healing in CSDs, presenting an adjunctive strategy for bone regeneration.
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Affiliation(s)
- Irmak Duman
- Department of Periodontology, Institute of Health Sciences, Marmara University, Istanbul, Turkey
| | - Gamze Tanrıverdi
- Department of Histology and Embryology, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Hafize Öztürk Özener
- Department of Periodontology, Faculty of Dentistry, Marmara University, Istanbul, Turkey
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Wang T, Xiong K, He Y, Feng B, Guo L, Gu J, Zhang M, Wang H, Wu X. Chronic pancreatitis-associated metabolic bone diseases: epidemiology, mechanisms, and clinical advances. Am J Physiol Endocrinol Metab 2024; 326:E856-E868. [PMID: 38656128 DOI: 10.1152/ajpendo.00113.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/11/2024] [Accepted: 04/17/2024] [Indexed: 04/26/2024]
Abstract
Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attention in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs. At the molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required to understand the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.
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Affiliation(s)
- Tianlin Wang
- Department of Emergency, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ke Xiong
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yanli He
- Department of General Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Binbin Feng
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - LinBin Guo
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jingliang Gu
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Mengrui Zhang
- Quantitative Sciences Unit, Department of Medicine, Stanford University, Stanford, California, United States
- Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States
- Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States
| | - Hong Wang
- Department of General Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaohao Wu
- Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States
- Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States
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Fawzy El-Sayed KM, Cosgarea R, Sculean A, Doerfer C. Can vitamins improve periodontal wound healing/regeneration? Periodontol 2000 2024; 94:539-602. [PMID: 37592831 DOI: 10.1111/prd.12513] [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: 05/12/2023] [Revised: 07/13/2023] [Accepted: 07/19/2023] [Indexed: 08/19/2023]
Abstract
Periodontitis is a complex inflammatory disorder of the tooth supporting structures, associated with microbial dysbiosis, and linked to a number if systemic conditions. Untreated it can result in an irreversible damage to the periodontal structures and eventually teeth loss. Regeneration of the lost periodontium requires an orchestration of a number of biological events on cellular and molecular level. In this context, a set of vitamins have been advocated, relying their beneficial physiological effects, to endorse the biological regenerative events of the periodontium on cellular and molecular levels. The aim of the present article is to elaborate on the question whether or not vitamins improve wound healing/regeneration, summarizing the current evidence from in vitro, animal and clinical studies, thereby shedding light on the knowledge gap in this field and highlighting future research needs. Although the present review demonstrates the current heterogeneity in the available evidence and knowledge gaps, findings suggest that vitamins, especially A, B, E, and CoQ10, as well as vitamin combinations, could exert positive attributes on the periodontal outcomes in adjunct to surgical or nonsurgical periodontal therapy.
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Affiliation(s)
- Karim M Fawzy El-Sayed
- Oral Medicine and Periodontology Department, Faculty of Oral and Dental Medicine, Cairo University, Giza, Egypt
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
| | - Raluca Cosgarea
- Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany
- Department of Periodontology and Peri-implant Diseases, Philips University Marburg, Marburg, Germany
- Clinic for Prosthetic Dentistry, University Iuliu-Hatieganu, Cluj-Napoca, Romania
| | - Anton Sculean
- Department of Periodontology, University of Bern, Bern, Switzerland
| | - Christof Doerfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, Kiel, Germany
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Wang H, Ma Y. The Potential of Vitamin K as a Regulatory Factor of Bone Metabolism-A Review. Nutrients 2023; 15:4935. [PMID: 38068793 PMCID: PMC10708186 DOI: 10.3390/nu15234935] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 11/23/2023] [Accepted: 11/27/2023] [Indexed: 12/18/2023] Open
Abstract
Vitamin K (VK), a fat-soluble vitamin, is essential for the clotting of blood because of its role in the production of clotting factors in the liver. Moreover, researchers continue to explore the role of VK as an emerging novel bioactive molecule with the potential function of improving bone health. This review focuses on the effects of VK on bone health and related mechanisms, covering VK research history, homologous analogs, dietary sources, bioavailability, recommended intake, and deficiency. The information summarized here could contribute to the basic and clinical research on VK as a natural dietary additive and drug candidate for bone health. Future research is needed to extend the dietary VK database and explore the pharmacological safety of VK and factors affecting VK bioavailability to provide more support for the bone health benefits of VK through more clinical trials.
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Affiliation(s)
- Huakai Wang
- Department of Animal Nutrition and Feed Science, State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China;
- Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences, Nongkenan Road No. 40, Hefei 230031, China
| | - Yongxi Ma
- Department of Animal Nutrition and Feed Science, State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China;
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Vahidi G, Moody M, Welhaven HD, Davidson L, Rezaee T, Behzad R, Karim L, Roggenbeck BA, Walk ST, Martin SA, June RK, Heveran CM. Germ-Free C57BL/6 Mice Have Increased Bone Mass and Altered Matrix Properties but Not Decreased Bone Fracture Resistance. J Bone Miner Res 2023; 38:1154-1174. [PMID: 37221143 PMCID: PMC10530360 DOI: 10.1002/jbmr.4835] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 05/02/2023] [Accepted: 05/12/2023] [Indexed: 05/25/2023]
Abstract
The gut microbiome impacts bone mass, which implies a disruption to bone homeostasis. However, it is not yet clear how the gut microbiome affects the regulation of bone mass and bone quality. We hypothesized that germ-free (GF) mice have increased bone mass and decreased bone toughness compared with conventionally housed mice. We tested this hypothesis using adult (20- to 21-week-old) C57BL/6J GF and conventionally raised female and male mice (n = 6-10/group). Trabecular microarchitecture and cortical geometry were measured from micro-CT of the femur distal metaphysis and cortical midshaft. Whole-femur strength and estimated material properties were measured using three-point bending and notched fracture toughness. Bone matrix properties were measured for the cortical femur by quantitative back-scattered electron imaging and nanoindentation, and, for the humerus, by Raman spectroscopy and fluorescent advanced glycation end product (fAGE) assay. Shifts in cortical tissue metabolism were measured from the contralateral humerus. GF mice had reduced bone resorption, increased trabecular bone microarchitecture, increased tissue strength and decreased whole-bone strength that was not explained by differences in bone size, increased tissue mineralization and fAGEs, and altered collagen structure that did not decrease fracture toughness. We observed several sex differences in GF mice, most notably for bone tissue metabolism. Male GF mice had a greater signature of amino acid metabolism, and female GF mice had a greater signature of lipid metabolism, exceeding the metabolic sex differences of the conventional mice. Together, these data demonstrate that the GF state in C57BL/6J mice alters bone mass and matrix properties but does not decrease bone fracture resistance. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
- Ghazal Vahidi
- Department of Mechanical & Industrial Engineering; Montana State University, Bozeman MT 59717
| | - Maya Moody
- Department of Chemistry & Biochemistry; Montana State University, Bozeman MT 59717
| | - Hope D. Welhaven
- Department of Chemistry & Biochemistry; Montana State University, Bozeman MT 59717
| | - Leah Davidson
- Department of Chemical and Biological Engineering; University of Idaho, Moscow ID 83844
| | - Taraneh Rezaee
- Department of Bioengineering; University of Massachusetts, Dartmouth, MA 02747
| | - Ramina Behzad
- Department of Bioengineering; University of Massachusetts, Dartmouth, MA 02747
| | - Lamya Karim
- Department of Bioengineering; University of Massachusetts, Dartmouth, MA 02747
| | - Barbara A. Roggenbeck
- Department of Microbiology & Cell Biology, Montana State University; Bozeman MT 59717
| | - Seth T. Walk
- Department of Microbiology & Cell Biology, Montana State University; Bozeman MT 59717
| | - Stephan A. Martin
- Translational Biomarkers Core Laboratory; Center for American Indian and Rural Health Equity; Montana State University, Bozeman MT 59717
| | - Ronald K. June
- Department of Mechanical & Industrial Engineering; Montana State University, Bozeman MT 59717
| | - Chelsea M. Heveran
- Department of Mechanical & Industrial Engineering; Montana State University, Bozeman MT 59717
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Yuan Y, Szeto IMY, Li N, Yang H, Zhou Y, Liu B, He F, Zhang L, Duan S, Chen J. Effects of Menaquinone-7 on the Bone Health of Growing Rats under Calcium Restriction: New Insights from Microbiome-Metabolomics. Nutrients 2023; 15:3398. [PMID: 37571336 PMCID: PMC10421271 DOI: 10.3390/nu15153398] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
Insufficient calcium intake during growth is a global public health concern. The aim of this study was to investigate the effects of dietary menaquinone-7 (MK-7) on bone accrual in growing Sprague-Dawley rats under calcium restriction. Following 13 weeks of treatment, various bone quality parameters, including microarchitecture, were measured. Fecal and cecal samples were subjected to microbiome (16S rRNA gene sequencing) analyses, while metabolomics analysis of the cecum and humerus samples was analyzed based on UHPLC-Q/TOF-MS. We found that calcium deficiency diminished the richness of the microbiome and disrupted microbiome composition, accompanied by an elevation in the relative abundance of Parasutterella. Furthermore, calcium insufficiency escalated the level of isovaleric acid and modified the metabolic profiles. MK-7 supplementation significantly increased the cortical thickness, cortical bone area, and the calcium content of the femur. Apart from improving bone calcium deposition and diminishing bone resorption, the mechanisms underlying the beneficial effects of MK on bone quality also involve the modulation of the host's metabolic pathways and the composition of gut microbiota. The gut-bone axis holds promise as an efficacious target for ameliorating calcium deficiency in children's bone quality, and MK-7 is a promising dietary supplement from this perspective.
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Affiliation(s)
- Ya Yuan
- Department of Nutrition and Food Safety, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; (Y.Y.); (N.L.); (Y.Z.); (F.H.); (L.Z.)
- School of Laboratory Medicine, Chengdu Medical College, Chengdu 610500, China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu 610041, China
| | - Ignatius Man-Yau Szeto
- Yili Maternal and Infant Nutrition Institute (YMINI), Inner Mongolia Yili Industrial Group, Co., Ltd., Beijing 100071, China; (I.M.-Y.S.); (B.L.)
- Inner Mongolia Dairy Technology Research Institute Co., Ltd., Hohhot 010110, China
- National Center of Technology Innovation for Dairy, Hohhot 013757, China
| | - Na Li
- Department of Nutrition and Food Safety, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; (Y.Y.); (N.L.); (Y.Z.); (F.H.); (L.Z.)
- Department of Nutrition, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Hua Yang
- The Analysis and Assay Center of Sichuan University West China School of Public Health, Sichuan University, Chengdu 610093, China;
| | - Yunzheng Zhou
- Department of Nutrition and Food Safety, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; (Y.Y.); (N.L.); (Y.Z.); (F.H.); (L.Z.)
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu 610041, China
| | - Biao Liu
- Yili Maternal and Infant Nutrition Institute (YMINI), Inner Mongolia Yili Industrial Group, Co., Ltd., Beijing 100071, China; (I.M.-Y.S.); (B.L.)
- Inner Mongolia Dairy Technology Research Institute Co., Ltd., Hohhot 010110, China
| | - Fang He
- Department of Nutrition and Food Safety, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; (Y.Y.); (N.L.); (Y.Z.); (F.H.); (L.Z.)
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu 610041, China
| | - Lishi Zhang
- Department of Nutrition and Food Safety, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; (Y.Y.); (N.L.); (Y.Z.); (F.H.); (L.Z.)
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu 610041, China
| | - Sufang Duan
- Yili Maternal and Infant Nutrition Institute (YMINI), Inner Mongolia Yili Industrial Group, Co., Ltd., Beijing 100071, China; (I.M.-Y.S.); (B.L.)
- Inner Mongolia Dairy Technology Research Institute Co., Ltd., Hohhot 010110, China
- National Center of Technology Innovation for Dairy, Hohhot 013757, China
| | - Jinyao Chen
- Department of Nutrition and Food Safety, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; (Y.Y.); (N.L.); (Y.Z.); (F.H.); (L.Z.)
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu 610041, China
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Xu J, Chen C, Gan S, Liao Y, Fu R, Hou C, Yang S, Zheng Z, Chen W. The Potential Value of Probiotics after Dental Implant Placement. Microorganisms 2023; 11:1845. [PMID: 37513016 PMCID: PMC10383117 DOI: 10.3390/microorganisms11071845] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/15/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
Dental implantation is currently the optimal solution for tooth loss. However, the health and stability of dental implants have emerged as global public health concerns. Dental implant placement, healing of the surgical site, osseointegration, stability of bone tissues, and prevention of peri-implant diseases are challenges faced in achieving the long-term health and stability of implants. These have been ongoing concerns in the field of oral implantation. Probiotics, as beneficial microorganisms, play a significant role in the body by inhibiting pathogens, promoting bone tissue homeostasis, and facilitating tissue regeneration, modulating immune-inflammatory levels. This review explores the potential of probiotics in addressing post-implantation challenges. We summarize the existing research regarding the importance of probiotics in managing dental implant health and advocate for further research into their potential applications.
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Affiliation(s)
- Jia Xu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Chenfeng Chen
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of General Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Shuaiqi Gan
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Yihan Liao
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Ruijie Fu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Chuping Hou
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Shuhan Yang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Zheng Zheng
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Wenchuan Chen
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Jinjiang Out-Patient Section, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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Ariano A, Posa F, Storlino G, Mori G. Molecules Inducing Dental Stem Cells Differentiation and Bone Regeneration: State of the Art. Int J Mol Sci 2023; 24:9897. [PMID: 37373044 DOI: 10.3390/ijms24129897] [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: 04/26/2023] [Revised: 05/30/2023] [Accepted: 06/05/2023] [Indexed: 06/29/2023] Open
Abstract
Teeth include mesenchymal stem cells (MSCs), which are multipotent cells that promote tooth growth and repair. Dental tissues, specifically the dental pulp and the dental bud, constitute a relevant source of multipotent stem cells, known as dental-derived stem cells (d-DSCs): dental pulp stem cells (DPSCs) and dental bud stem cells (DBSCs). Cell treatment with bone-associated factors and stimulation with small molecule compounds are, among the available methods, the ones who show excellent advantages promoting stem cell differentiation and osteogenesis. Recently, attention has been paid to studies on natural and non-natural compounds. Many fruits, vegetables, and some drugs contain molecules that can enhance MSC osteogenic differentiation and therefore bone formation. The purpose of this review is to examine research work over the past 10 years that has investigated two different types of MSCs from dental tissues that are attractive targets for bone tissue engineering: DPSCs and DBSCs. The reconstruction of bone defects, in fact, is still a challenge and therefore more research is needed; the articles reviewed are meant to identify compounds useful to stimulate d-DSC proliferation and osteogenic differentiation. We only consider the results of the research which is encouraging, assuming that the mentioned compounds are of some importance for bone regeneration.
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Affiliation(s)
- Anastasia Ariano
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy
| | - Francesca Posa
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy
| | - Giuseppina Storlino
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy
| | - Giorgio Mori
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy
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Chuai Y, Dai B, Liu X, Hu M, Wang Y, Zhang H. Association of vitamin K, fibre intake and progression of periodontal attachment loss in American adults. BMC Oral Health 2023; 23:303. [PMID: 37198606 DOI: 10.1186/s12903-023-02929-9] [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: 01/19/2023] [Accepted: 04/01/2023] [Indexed: 05/19/2023] Open
Abstract
BACKGROUND Periodontitis-related attachment loss is accompanied by mucosal bleeding and inflammatory lesions. Dietary vitamin K and fibre intake are known to be correlation factors of haemostasis and anti-inflammation, respectively. OBJECTIVE To explore the association between severe periodontal attachment loss and vitamin K or fibre intake in American adults. METHODS A cross-sectional analysis was conducted including 2747 males and 2218 females in the National Health and Nutrition Examination Surveys (NHANES) from 2009 to 2014. The number of teeth with severe periodontal attachment loss (above 5 mm attachment loss) was used as the dependent variable. The main independent variables included the intake of vitamin K and dietary fibre. The association among variables was examined using multivariable linear regression models, hierarchical regression, fitted smoothing curves, and generalized additive models. RESULTS Based on the indicators of 4965 subjects, we found that severe attachment loss tended to occur in elderly individuals or males and was accompanied by less intake of vitamin K or dietary fibre, as well as lower educational qualification. Vitamin K intake was stably negatively associated with attachment loss progression in each multivariable linear regression model. In subgroup analyses, a negative association between fibre intake and attachment loss progression was identified in all races except blacks (β = 0.0005, 95% CI: -0.0005 to 0.0016). The relationship between fibre intake and attachment loss progression was a broad U-shaped curve (inflection point: 753.4 mg), which especially manifested in males (inflection point: 967.5 mg). CONCLUSION There was an inverse association between vitamin K intake and the progression of periodontal attachment loss in American adults, while dietary fibre should be moderate in intake (below 753.4 mg), especially in males (below 967.5 mg).
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Affiliation(s)
- Yuanyuan Chuai
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Bichong Dai
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Xiaoyun Liu
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Menglin Hu
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China
| | - Yuanyin Wang
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China.
- Department of Oral and Maxillofacial Surgery, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China.
| | - Hengguo Zhang
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China.
- Department of Dental Implantology, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China.
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10
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Knowles HJ, Chanalaris A, Koutsikouni A, Cribbs AP, Grover LM, Hulley PA. Mature primary human osteocytes in mini organotypic cultures secrete FGF23 and PTH1-34-regulated sclerostin. Front Endocrinol (Lausanne) 2023; 14:1167734. [PMID: 37223031 PMCID: PMC10200954 DOI: 10.3389/fendo.2023.1167734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 04/03/2023] [Indexed: 05/25/2023] Open
Abstract
Introduction For decades, functional primary human osteocyte cultures have been crucially needed for understanding their role in bone anabolic processes and in endocrine phosphate regulation via the bone-kidney axis. Mature osteocyte proteins (sclerostin, DMP1, Phex and FGF23) play a key role in various systemic diseases and are targeted by successful bone anabolic drugs (anti-sclerostin antibody and teriparatide (PTH1-34)). However, cell lines available to study osteocytes produce very little sclerostin and low levels of mature osteocyte markers. We have developed a primary human 3D organotypic culture system that replicates the formation of mature osteocytes in bone. Methods Primary human osteoblasts were seeded in a fibrinogen / thrombin gel around 3D-printed hanging posts. Following contraction of the gel around the posts, cells were cultured in osteogenic media and conditioned media was collected for analysis of secreted markers of osteocyte formation. Results The organoids were viable for at least 6 months, allowing co-culture with different cell types and testing of bone anabolic drugs. Bulk RNAseq data displayed the developing marker trajectory of ossification and human primary osteocyte formation in vitro over an initial 8- week period. Vitamin D3 supplementation increased mineralization and sclerostin secretion, while hypoxia and PTH1-34 modulated sclerostin. Our culture system also secreted FGF23, enabling the future development of a bone-kidney-parathyroid-vascular multi-organoid or organ-on-a-chip system to study disease processes and drug effects using purely human cells. Discussion This 3D organotypic culture system provides a stable, long-lived, and regulated population of mature human primary osteocytes for a variety of research applications.
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Affiliation(s)
- Helen J. Knowles
- Botnar Institute for Musculoskeletal Sciences, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
| | - Anastasios Chanalaris
- Botnar Institute for Musculoskeletal Sciences, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
| | - Argyro Koutsikouni
- School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Adam P. Cribbs
- Botnar Institute for Musculoskeletal Sciences, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
- Oxford Centre for Translational Myeloma Research, Botnar Institute for Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
| | - Liam M. Grover
- Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Birmingham, United Kingdom
| | - Philippa A. Hulley
- Botnar Institute for Musculoskeletal Sciences, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
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11
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Jackova Z, Stepan JJ, Coufal S, Kostovcik M, Galanova N, Reiss Z, Pavelka K, Wenchich L, Hruskova H, Kverka M. Interindividual differences contribute to variation in microbiota composition more than hormonal status: A prospective study. Front Endocrinol (Lausanne) 2023; 14:1139056. [PMID: 37033235 PMCID: PMC10081494 DOI: 10.3389/fendo.2023.1139056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 02/13/2023] [Indexed: 04/11/2023] Open
Abstract
Aims Ovarian hormone deficiency is one of the main risk factors for osteoporosis and bone fractures in women, and these risks can be mitigated by menopausal hormone therapy. Recent evidence suggests that gut microbiota may link changes in estrogen levels and bone metabolism. This study was conducted to investigate the potential relationship between hormonal and bone changes induced by oophorectomy and subsequent hormonal therapy and shifts in gut microbiota composition. Methods We collected 159 stool and blood samples in several intervals from 58 women, who underwent bilateral oophorectomy. Changes in fecal microbiota were assessed in paired samples collected from each woman before and after oophorectomy or the start of hormone therapy. Bacterial composition was determined by sequencing the 16S rRNA gene on Illumina MiSeq. Blood levels of estradiol, FSH, biomarkers of bone metabolism, and indices of low-grade inflammation were measured using laboratory analytical systems and commercial ELISA. Areal bone mineral density (BMD) of the lumbar spine, proximal femur, and femur neck was measured using dual-energy X-ray absorptiometry. Results We found no significant changes in gut microbiota composition 6 months after oophorectomy, despite major changes in hormone levels, BMD, and bone metabolism. A small decrease in bacterial diversity was apparent 18 months after surgery in taxonomy-aware metrics. Hormonal therapy after oophorectomy prevented bone loss but only marginally affected gut microbiota. There were no significant differences in β-diversity related to hormonal status, although several microbes (e.g., Lactococcus lactis) followed estrogen levels. Body mass index (BMI) was the most significantly associated with microbiota variance. Microbiota was not a suitable predictive factor for the state of bone metabolism. Conclusions We conclude that neither the loss of estrogens due to oophorectomy nor their gain due to subsequent hormonal therapy is associated with a specific gut microbiota signature. Sources of variability in microbiota composition are more related to interindividual differences than hormonal status.
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Affiliation(s)
- Zuzana Jackova
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czechia
| | - Jan J. Stepan
- Institute of Rheumatology, Prague, Czechia
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | - Stepan Coufal
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czechia
| | - Martin Kostovcik
- Laboratory of Fungal Genetics and Metabolism, Institute of Microbiology, Czech Academy of Sciences, Prague, Czechia
| | - Natalie Galanova
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czechia
| | - Zuzana Reiss
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czechia
| | - Karel Pavelka
- Institute of Rheumatology, Prague, Czechia
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | | | - Hana Hruskova
- Department of Obstetrics and Gynecology, Charles University in Prague, First Faculty of Medicine, Prague, Czechia
- General University Hospital in Prague, Prague, Czechia
| | - Miloslav Kverka
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czechia
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12
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Alonso N, Meinitzer A, Fritz-Petrin E, Enko D, Herrmann M. Role of Vitamin K in Bone and Muscle Metabolism. Calcif Tissue Int 2023; 112:178-196. [PMID: 35150288 PMCID: PMC9859868 DOI: 10.1007/s00223-022-00955-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 01/26/2022] [Indexed: 01/25/2023]
Abstract
Vitamin K, a cofactor for the γ-glutamyl carboxylase enzyme, is required for the post-translational activation of osteocalcin and matrix Gla protein, which play a key role in bone and muscle homeostasis. In vivo and in vitro models for osteoporosis and sarcopenia suggest the vitamin K could exert a positive effect in both conditions. In bone, it increases osteoblastogenesis, whilst decreases osteoclast formation and function. In muscle, it is associated with increased satellite cell proliferation and migration and might play a role in energy metabolism. Observational trials suggest that high levels of vitamin K are associated with increased bone mineral density and reduced fracture risk. However, interventional studies for vitamin K supplementation yielded conflicting results. Clinical trials in sarcopenia suggest that vitamin K supplementation could improve muscle mass and function. One of the main limitations on the vitamin K studies are the technical challenges to measure its levels in serum. Thus, they are obtained from indirect sources like food questionnaires, or levels of undercarboxylated proteins, which can be affected by other environmental or biological processes. Although current research appoints to a beneficial effect of vitamin K in bone and muscle, further studies overcoming the current limitations are required in order to incorporate this supplementation in the clinical management of patients with osteosarcopenia.
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Affiliation(s)
- N Alonso
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - A Meinitzer
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - E Fritz-Petrin
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - D Enko
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - M Herrmann
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
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13
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Sojan JM, Licini C, Marcheggiani F, Carnevali O, Tiano L, Mattioli-Belmonte M, Maradonna F. Bacillus subtilis Modulated the Expression of Osteogenic Markers in a Human Osteoblast Cell Line. Cells 2023; 12:cells12030364. [PMID: 36766709 PMCID: PMC9913848 DOI: 10.3390/cells12030364] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 01/12/2023] [Accepted: 01/13/2023] [Indexed: 01/20/2023] Open
Abstract
Several in vivo trials have previously demonstrated the beneficial effects of the administration of various probiotic forms on bone health. In this study, we explored the potency of two probiotics, Bacillus subtilis and Lactococcus lactis, alone or in combination with vitamin D (VD), to modulate the transcription of genes involved in the ossification process in a human osteoblast cell line. Genes that mark the "osteoblast proliferation phase", such as RUNX2, TGFB1, and ALPL, "extracellular matrix (ECM) maturation", such as SPP1 and SPARC, as well as "ECM mineralization", such as BGN, BGLAP, and DCN, were all highly expressed in osteoblasts treated with B. subtilis extract. The observed increase in the transcription of the ALPL mRNA was further in agreement with its protein levels as observed by Western blot and immunofluorescence. Therefore, this higher transcription and translation of alkaline phosphatase in osteoblasts treated with the B. subtilis extract, indicated its substantial osteogenic impact on human osteoblasts. Although both the probiotic extracts showed no osteogenic synergy with VD, treatment with B. subtilis alone could increase the ECM mineralization, outperforming the effects of L. lactis and even VD. Furthermore, these results supported the validity of employing probiotic extracts rather than live cells to investigate the effects of probiotics in the in vitro systems.
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Affiliation(s)
- Jerry Maria Sojan
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy
| | - Caterina Licini
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Via Tronto 10/a, 60126 Ancona, Italy
| | - Fabio Marcheggiani
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy
| | - Oliana Carnevali
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy
- Correspondence: (O.C.); (F.M.); Tel.: +39-0712204990 (O.C.)
| | - Luca Tiano
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy
| | - Monica Mattioli-Belmonte
- Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Via Tronto 10/a, 60126 Ancona, Italy
| | - Francesca Maradonna
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy
- Correspondence: (O.C.); (F.M.); Tel.: +39-0712204990 (O.C.)
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14
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Huang R, Liu P, Bai Y, Huang J, Pan R, Li H, Su Y, Zhou Q, Ma R, Zong S, Zeng G. Changes in the gut microbiota of osteoporosis patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis. J Zhejiang Univ Sci B 2022; 23:1002-1013. [PMID: 36518053 PMCID: PMC9758719 DOI: 10.1631/jzus.b2200344] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 08/11/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND: Osteoporosis (OP) has become a major public health issue, threatening the bone health of middle-aged and elderly people from all around the world. Changes in the gut microbiota (GM) are correlated with the maintenance of bone mass and bone quality. However, research results in this field remain highly controversial, and no systematic review or meta-analysis of the relationship between GM and OP has been conducted. This paper addresses this shortcoming, focusing on the difference in the GM abundance between OP patients and healthy controls based on previous 16S ribosomal RNA (rRNA) gene sequencing results, in order to provide new clinical reference information for future customized prevention and treatment options of OP. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI). In addition, we applied the R programming language version 4.0.3 and Stata 15.1 software for data analysis. We also implemented the Newcastle-Ottawa Scale (NOS), funnel plot analysis, sensitivity analysis, Egger's test, and Begg's test to assess the risk of bias. RESULTS: This research ultimately considered 12 studies, which included the fecal GM data of 2033 people (604 with OP and 1429 healthy controls). In the included research papers, it was observed that the relative abundance of Lactobacillus and Ruminococcus increased in the OP group, while the relative abundance for Bacteroides of Bacteroidetes increased (except for Ireland). Meanwhile, Firmicutes, Blautia, Alistipes, Megamonas, and Anaerostipes showed reduced relative abundance in Chinese studies. In the linear discriminant analysis Effect Size (LEfSe) analysis, certain bacteria showed statistically significant results consistently across different studies. CONCLUSIONS: This observational meta-analysis revealed that changes in the GM were correlated with OP, and variations in some advantageous GM might involve regional differences.
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Affiliation(s)
- Rui Huang
- College of Public Hygiene of Guangxi Medical University, Nanning 530021, China
| | - Pan Liu
- Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
- Department of Orthopaedics, the Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, China
| | - Yiguang Bai
- Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
- Department of Orthopaedics, Nanchong Central Hospital, the Second Clinical Institute of North Sichuan Medical College, Nanchong 637000, China
| | - Jieqiong Huang
- College of Public Hygiene of Guangxi Medical University, Nanning 530021, China
| | - Rui Pan
- College of Public Hygiene of Guangxi Medical University, Nanning 530021, China
| | - Huihua Li
- College of Public Hygiene of Guangxi Medical University, Nanning 530021, China
| | - Yeping Su
- College of Public Hygiene of Guangxi Medical University, Nanning 530021, China
| | - Quan Zhou
- Department of Wound Repair, the First People's Hospital of Nanning, Nanning 530022, China
| | - Ruixin Ma
- Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Shaohui Zong
- Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
| | - Gaofeng Zeng
- College of Public Hygiene of Guangxi Medical University, Nanning 530021, China. ,
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15
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Ziemińska M, Pawlak D, Sieklucka B, Chilkiewicz K, Pawlak K. Vitamin K-Dependent Carboxylation of Osteocalcin in Bone-Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease? Nutrients 2022; 14:nu14194082. [PMID: 36235734 PMCID: PMC9572286 DOI: 10.3390/nu14194082] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 09/27/2022] [Accepted: 09/27/2022] [Indexed: 11/09/2022] Open
Abstract
Chronic kidney disease (CKD) commonly occurs with vitamin K (VK) deficiency and impaired bone mineralization. However, there are no data explaining the metabolism of endogenous VK and its role in bone mineralization in CKD. In this study, we measured serum levels of phylloquinone (VK1), menaquinone 4 and 7 (MK4, MK7), and VK-dependent proteins: osteocalcin, undercarboxylated osteocalcin (Glu-OC), and undercarboxylated matrix Gla protein (ucMGP). The carboxylated osteocalcin (Gla-OC), Glu-OC, and the expression of genes involved in VK cycle were determined in bone. The obtained results were juxtaposed with the bone mineral status of rats with CKD. The obtained results suggest that the reduced VK1 level observed in CKD rats may be caused by the accelerated conversion of VK1 to the form of menaquinones. The bone tissue possesses all enzymes, enabling the conversion of VK1 to menaquinones and VK recycling. However, in the course of CKD with hyperparathyroidism, the intensified osteoblastogenesis causes the generation of immature osteoblasts with impaired mineralization. The particular clinical significance seems to have a finding that serum osteocalcin and Glu-OC, commonly used biomarkers of VK deficiency, could be inappropriate in CKD conditions, whereas Gla-OC synthesized in bone appears to have an adverse impact on bone mineral status in this model.
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Affiliation(s)
- Marta Ziemińska
- Department of Monitored Pharmacotherapy, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, Poland
| | - Dariusz Pawlak
- Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, Poland
| | - Beata Sieklucka
- Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, Poland
| | - Katarzyna Chilkiewicz
- Department of Monitored Pharmacotherapy, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, Poland
| | - Krystyna Pawlak
- Department of Monitored Pharmacotherapy, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, Poland
- Correspondence: ; Tel.: +48-85-7485600
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16
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Sim M, Strydom A, Blekkenhorst LC, Bondonno NP, McCormick R, Lim WH, Zhu K, Byrnes E, Hodgson JM, Lewis JR, Prince RL. Dietary Vitamin K1 intake is associated with lower long-term fracture-related hospitalization risk: the Perth longitudinal study of ageing women. Food Funct 2022; 13:10642-10650. [PMID: 36169025 DOI: 10.1039/d2fo02494b] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
This study examined the association between dietary Vitamin K1 intake with fracture-related hospitalizations over 14.5 years in community-dwelling older Australian women (n = 1373, ≥70 years). Dietary Vitamin K1 intake at baseline (1998) was estimated using a validated food frequency questionnaire and a new Australian Vitamin K nutrient database, which was supplemented with published data. Over 14.5 years, any fracture (n = 404, 28.3%) and hip fracture (n = 153, 10.7%) related hospitalizations were captured using linked health data. Plasma Vitamin D status (25OHD) and the ratio of undercarboxylated osteocalcin (ucOC) to total osteocalcin (tOC) from serum was assessed at baseline. Estimates of dietary Vitamin K1 intake were supported by a significant inverse association with ucOC : tOC; a marker of Vitamin K status (r = -0.12, p < 0.001). Compared to women with the lowest Vitamin K1 intake (Quartile 1, <61 μg d-1), women with the highest Vitamin K1 intake (Quartile 4, ≥99 μg d-1) had lower hazards for any fracture- (HR 0.69 95%CI 0.52-0.91, p < 0.001) and hip fracture-related hospitalization (HR 0.51 95%CI 0.32-0.79, p < 0.001), independent of 25OHD levels, as part of multivariable-adjusted analysis. Spline analysis suggested a nadir in the relative hazard for any fracture-related hospitalizations at a Vitamin K1 intake of approximately 100 μg day-1. For hip fractures, a similar relationship was apparent. Higher dietary Vitamin K1 is associated with lower long-term risk for any fracture- and hip fracture-related hospitalizations in community-dwelling older women.
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Affiliation(s)
- Marc Sim
- Nutrition & Health Innovation Research Institute, School of Health and Medical Sciences, Edith Cowan University, Perth, Western Australia, Australia. .,Medical School, The University of Western Australia, Perth, Western Australia, Australia.,Royal Perth Hospital Research Foundation, Perth, Western Australia, Australia
| | - Andre Strydom
- Medical School, The University of Western Australia, Perth, Western Australia, Australia
| | - Lauren C Blekkenhorst
- Nutrition & Health Innovation Research Institute, School of Health and Medical Sciences, Edith Cowan University, Perth, Western Australia, Australia. .,Medical School, The University of Western Australia, Perth, Western Australia, Australia.,Royal Perth Hospital Research Foundation, Perth, Western Australia, Australia
| | - Nicola P Bondonno
- Nutrition & Health Innovation Research Institute, School of Health and Medical Sciences, Edith Cowan University, Perth, Western Australia, Australia. .,Danish Cancer Society, Copenhagen, Denmark
| | - Rachel McCormick
- Nutrition & Health Innovation Research Institute, School of Health and Medical Sciences, Edith Cowan University, Perth, Western Australia, Australia.
| | - Wai H Lim
- Medical School, The University of Western Australia, Perth, Western Australia, Australia.,Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia
| | - Kun Zhu
- Medical School, The University of Western Australia, Perth, Western Australia, Australia.,Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Elizabeth Byrnes
- Department of Clinical Biochemistry, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, Australia
| | - Jonathan M Hodgson
- Nutrition & Health Innovation Research Institute, School of Health and Medical Sciences, Edith Cowan University, Perth, Western Australia, Australia. .,Medical School, The University of Western Australia, Perth, Western Australia, Australia.,Royal Perth Hospital Research Foundation, Perth, Western Australia, Australia
| | - Joshua R Lewis
- Nutrition & Health Innovation Research Institute, School of Health and Medical Sciences, Edith Cowan University, Perth, Western Australia, Australia. .,Medical School, The University of Western Australia, Perth, Western Australia, Australia.,Royal Perth Hospital Research Foundation, Perth, Western Australia, Australia.,Centre for Kidney Research, Children's Hospital at Westmead, School of Public Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
| | - Richard L Prince
- Nutrition & Health Innovation Research Institute, School of Health and Medical Sciences, Edith Cowan University, Perth, Western Australia, Australia. .,Medical School, The University of Western Australia, Perth, Western Australia, Australia.,Curtin University, School of Public Health, Perth, Western Australia, Australia
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17
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Ma ML, Ma ZJ, He YL, Sun H, Yang B, Ruan BJ, Zhan WD, Li SX, Dong H, Wang YX. Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials. Front Public Health 2022; 10:979649. [PMID: 36033779 PMCID: PMC9403798 DOI: 10.3389/fpubh.2022.979649] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 07/21/2022] [Indexed: 01/25/2023] Open
Abstract
Introduction Vitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone strength. However, some studies have been inconsistent on whether vitamin K2 (VK2) can maintain or improve bone mineral density (BMD) and reduce the incidence of fractures in postmenopausal women. Therefore, the main objective of this meta-analysis was to determine the effect of VK2 as a nutritional supplement on BMD and fracture incidence in postmenopausal women. Methods We searched PubMed, EMBASE, and Cochrane Library databases (published before March 17, 2022) and then extracted and pooled data from all randomized controlled trials (RCTs) that met the inclusion criteria. Results Sixteen RCTs with a total of 6,425 subjects were included in this meta-analysis. The overall effect test of 10 studies showed a significant improvement in lumbar spine BMD (BMD LS) (P = 0.006) with VK2. The subgroup analysis of VK2 combination therapy showed that BMD LS was significantly maintained and improved with the administration of VK2 (P = 0.03). The overall effect test of the six RCTs showed no significant difference in fracture incidence between the two groups (RR=0.96, P=0.65). However, after excluding one heterogeneous study, the overall effect test showed a significant reduction in fracture incidence with VK2 (RR = 0.43, P = 0.01). In addition, this meta-analysis showed that VK2 reduced serum undercarboxylated osteocalcin (uc-OC) levels and the ratio of uc-OC to cOC in both subgroups of VK2 combined intervention and alone. However, for carboxylated osteocalcin (cOC), both subgroup analysis and overall effect test showed no significant effect of VK2 on it. And the pooled analysis of adverse reactions showed no significant difference between the VK2 and control groups (RR = 1.03, 95%CI 0.87 to 1.21, P = 0.76). Conclusions The results of this meta-analysis seem to indicate that VK2 supplementation has a positive effect on the maintenance and improvement of BMD LS in postmenopausal women, and it can also reduce the fracture incidence, serum uc-OC levels and the ratio of uc-OC to cOC. In conclusion, VK2 can indirectly promote bone mineralization and increase bone strength.
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Affiliation(s)
- Ming-ling Ma
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical Medical College, Yangzhou University, Yangzhou, China,Department of Graduate School, Dalian Medical University, Dalian, China
| | - Zi-jian Ma
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical Medical College, Yangzhou University, Yangzhou, China,Yangzhou University Medical College, Yangzhou, China
| | - Yi-lang He
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical Medical College, Yangzhou University, Yangzhou, China,Department of Graduate School, Dalian Medical University, Dalian, China
| | - Hao Sun
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Bin Yang
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical Medical College, Yangzhou University, Yangzhou, China,Yangzhou University Medical College, Yangzhou, China
| | - Bin-jia Ruan
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Wan-da Zhan
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical Medical College, Yangzhou University, Yangzhou, China,Yangzhou University Medical College, Yangzhou, China
| | - Shi-xuan Li
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical Medical College, Yangzhou University, Yangzhou, China,Department of Graduate School, Dalian Medical University, Dalian, China
| | - Hui Dong
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical Medical College, Yangzhou University, Yangzhou, China,Hui Dong
| | - Yong-xiang Wang
- Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical Medical College, Yangzhou University, Yangzhou, China,*Correspondence: Yong-xiang Wang
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18
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Pereira L, Monteiro R. Tailoring gut microbiota with a combination of Vitamin K and probiotics as a possible adjuvant in the treatment of rheumatic arthritis: a systematic review. Clin Nutr ESPEN 2022; 51:37-49. [DOI: 10.1016/j.clnesp.2022.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 06/14/2022] [Accepted: 08/01/2022] [Indexed: 10/15/2022]
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Lu J, Hu D, Ma C, Shuai B. Advances in Our Understanding of the Mechanism of Action of Drugs (including Traditional Chinese Medicines) for the Intervention and Treatment of Osteoporosis. Front Pharmacol 2022; 13:938447. [PMID: 35774616 PMCID: PMC9237325 DOI: 10.3389/fphar.2022.938447] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 05/23/2022] [Indexed: 12/12/2022] Open
Abstract
Osteoporosis (OP) is known as a silent disease in which the loss of bone mass and bone density does not cause obvious symptoms, resulting in insufficient treatment and preventive measures. The losses of bone mass and bone density become more severe over time and an only small percentage of patients are diagnosed when OP-related fractures occur. The high disability and mortality rates of OP-related fractures cause great psychological and physical damage and impose a heavy economic burden on individuals and society. Therefore, early intervention and treatment must be emphasized to achieve the overall goal of reducing the fracture risk. Anti-OP drugs are currently divided into three classes: antiresorptive agents, anabolic agents, and drugs with other mechanisms. In this review, research progress related to common anti-OP drugs in these three classes as well as targeted therapies is summarized to help researchers and clinicians understand their mechanisms of action and to promote pharmacological research and novel drug development.
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Probiotics Enhance Bone Growth and Rescue BMP Inhibition: New Transgenic Zebrafish Lines to Study Bone Health. Int J Mol Sci 2022; 23:ijms23094748. [PMID: 35563140 PMCID: PMC9102566 DOI: 10.3390/ijms23094748] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/21/2022] [Accepted: 04/22/2022] [Indexed: 02/07/2023] Open
Abstract
Zebrafish larvae, especially gene-specific mutants and transgenic lines, are increasingly used to study vertebrate skeletal development and human pathologies such as osteoporosis, osteopetrosis and osteoarthritis. Probiotics have been recognized in recent years as a prophylactic treatment for various bone health issues in humans. Here, we present two new zebrafish transgenic lines containing the coding sequences for fluorescent proteins inserted into the endogenous genes for sp7 and col10a1a with larvae displaying fluorescence in developing osteoblasts and the bone extracellular matrix (mineralized or non-mineralized), respectively. Furthermore, we use these transgenic lines to show that exposure to two different probiotics, Bacillus subtilis and Lactococcus lactis, leads to an increase in osteoblast formation and bone matrix growth and mineralization. Gene expression analysis revealed the effect of the probiotics, particularly Bacillus subtilis, in modulating several skeletal development genes, such as runx2, sp7, spp1 and col10a1a, further supporting their ability to improve bone health. Bacillus subtilis was the more potent probiotic able to significantly reverse the inhibition of bone matrix formation when larvae were exposed to a BMP inhibitor (LDN212854).
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Du J, He Z, Cui J, Li H, Xu M, Zhang S, Zhang S, Yan M, Qu X, Yu Z. Osteocyte Apoptosis Contributes to Cold Exposure-induced Bone Loss. Front Bioeng Biotechnol 2021; 9:733582. [PMID: 34858954 PMCID: PMC8632005 DOI: 10.3389/fbioe.2021.733582] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 09/27/2021] [Indexed: 12/19/2022] Open
Abstract
Emerging evidence indicates that bone mass is regulated by systemic energy balance. Temperature variations have profound effects on energy metabolism in animals, which will affect bone remodeling. But the mechanism remains unclear. 2-month-old C57BL/6J male mice were exposed to cold (4°C) and normal (23°C) temperatures for 28 days and the effects of cold exposure on bone mass was investigated. Micro-computed tomography results showed that bone volume fraction was significantly reduced after 14 days of exposure to cold temperature, and it was recovered after 28 days. Ploton silver staining and immunohistochemical results further revealed that exposure to cold decreased canalicular length, number of E11-and MMP13-positive osteocytes after 14 days, but they returned to the baseline levels after 28 days, different from the normal temperature control group. In addition, change of Caspase-3 indicated that exposure to cold temperature augmented apoptosis of osteocytes. In vitro results confirmed the positive effect of brown adipocytes on osteocyte‘s dendrites and E11 expression. In conclusion, our findings indicate that cold exposure can influence bone mass in a time-dependent manner, with bone mass decreasing and recovering at 2 and 4 weeks respectively. The change of bone mass may be caused by the apoptosis osteocytes. Brown adipocyte tissue could influence bone remodeling through affecting osteocyte.
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Affiliation(s)
- Jingke Du
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zihao He
- Arthritis Clinic and Research Center, Peking University People's Hospital, Peking University, Beijing, China
| | - Junqi Cui
- Department of Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hanjun Li
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mingming Xu
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shuhong Zhang
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shuangyan Zhang
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengning Yan
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xinhua Qu
- Department of Bone and Joint Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhifeng Yu
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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22
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Hu L, Ji J, Li D, Meng J, Yu B. The combined effect of vitamin K and calcium on bone mineral density in humans: a meta-analysis of randomized controlled trials. J Orthop Surg Res 2021; 16:592. [PMID: 34649591 PMCID: PMC8515712 DOI: 10.1186/s13018-021-02728-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 09/15/2021] [Indexed: 01/22/2023] Open
Abstract
Background With the increasing incidence of osteoporosis, vitamin K and calcium have been linked to bone mineral density (BMD) and undercarboxylated osteocalcin (UcOC) in many studies, but the results of studies of the combined effect of vitamin K and calcium on BMD and UcOC in humans have been inconsistent. We conducted a systematic review of randomized controlled trials to assess the effect of this combination treatment on BMD and UcOC in humans. Methods A search for articles was conducted using PubMed, Embase, and the Cochrane Library database up to March 2021 (no language restrictions). We also reviewed the reference lists of the relevant publications and reviews to locate additional publications. The standard mean difference (SMD) was used as the primary measure of effect size. Our main endpoints were lumbar BMD, femoral neck BMD, hip BMD, total femoral BMD, and UcOC from baseline to end point. We performed subgroup analysis, heterogeneity testing, and assessment of publication bias. Results A total of 1346 patients from 10 randomized controlled trials were included in the meta-analysis. The forest plot analysis revealed that vitamin K combined with calcium was associated with a higher lumbar spine BMD compared to controls. The SMD was 0.20 [95% confidence interval (CI): 0.07 to 0.32]. Vitamin K and calcium supplementation led to a significant decrease in UcOC (SMD: − 1.71, 95% CI: − 2.45 to − 0.96). Subgroup analysis showed that vitamin K2 and vitamin K1 had SMDs of 0.30 (95% CI: 0.10 to 0.51) and SMDs of 0.14 (95% CI: − 0.02 to 0.29), and calcium dosages of ≤ 1000 mg/d or > 1000 mg/d had SMDs of 0.19 (95% CI: 0.05 to 0.32) and 0.26 (95% CI: − 0.04 to 0.55). Conclusion The combination of vitamin K and calcium has a positive effect on lumbar BMD and decreases the level of UcOC. Registration: The protocol for this meta-analysis was registered at the International Prospective Register of Systematic Reviews (CRD42021251825).
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Affiliation(s)
- Liyou Hu
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Jindou Ji
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Dong Li
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Jing Meng
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Bo Yu
- Department of Orthopaedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jingshi Road 16369, Jinan, 250014, China.
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23
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Rodrigues FG, Ormanji MS, Heilberg IP, Bakker SJL, de Borst MH. Interplay between gut microbiota, bone health and vascular calcification in chronic kidney disease. Eur J Clin Invest 2021; 51:e13588. [PMID: 33948936 PMCID: PMC8459296 DOI: 10.1111/eci.13588] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/30/2021] [Accepted: 05/01/2021] [Indexed: 02/06/2023]
Abstract
Deregulations in gut microbiota may play a role in vascular and bone disease in chronic kidney disease (CKD). As glomerular filtration rate declines, the colon becomes more important as a site of excretion of urea and uric acid, and an increased bacterial proteolytic fermentation alters the gut microbial balance. A diet with limited amounts of fibre, as well as certain medications (eg phosphate binders, iron supplementation, antibiotics) further contribute to changes in gut microbiota composition among CKD patients. At the same time, both vascular calcification and bone disease are common in patients with advanced kidney disease. This narrative review describes emerging evidence on gut dysbiosis, vascular calcification, bone demineralization and their interrelationship termed the 'gut-bone-vascular axis' in progressive CKD. The role of diet, gut microbial metabolites (ie indoxyl sulphate, p-cresyl sulphate, trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFA)), vitamin K deficiency, inflammatory cytokines and their impact on both bone health and vascular calcification are discussed. This framework may open up novel preventive and therapeutic approaches targeting the microbiome in an attempt to improve cardiovascular and bone health in CKD.
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Affiliation(s)
- Fernanda G Rodrigues
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.,Nutrition Post-Graduation Program, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Milene S Ormanji
- Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Ita P Heilberg
- Nutrition Post-Graduation Program, Universidade Federal de São Paulo, São Paulo, Brazil.,Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Stephan J L Bakker
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Martin H de Borst
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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24
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Zhang Y, Zhang T, Liang Y, Jiang L, Sui X. Dietary Bioactive Lipids: A Review on Absorption, Metabolism, and Health Properties. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:8929-8943. [PMID: 34161727 DOI: 10.1021/acs.jafc.1c01369] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Dietary lipids are an indispensable source of energy and nutrition in human life. Numerous studies have shown that dietary bioactive lipids have many health benefits, including prevention or treatment of chronic diseases. The different chemical compositions and structural characteristics of bioactive lipids not only affect their digestion, absorption, and metabolism but also affect their health properties. In this review, the major dietary bioactive lipids (fatty acids, carotenoids, phytosterols, phenolic lipids, fat-soluble vitamins, and sphingomyelins) in foods are systematically summarized, from the aspects of composition, digestion, absorption, metabolism, source, structural characteristics, and their health properties. In particular, the relationship between the compositional and structural changes of bioactive lipids and their absorption and metabolism is discussed as well as their effect on health properties. This review provides a comprehensive summary toward health properties of dietary bioactive lipids.
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Affiliation(s)
- Yan Zhang
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
- College of Horticulture and Landscape Architecture, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
- National-Local Joint Engineering Research Center for Development and Utilization of Small Fruits in Cold Regions, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
| | - Tianyi Zhang
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
| | - Yan Liang
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
| | - Lianzhou Jiang
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
| | - Xiaonan Sui
- College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China
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Silva TR, Oppermann K, Reis FM, Spritzer PM. Nutrition in Menopausal Women: A Narrative Review. Nutrients 2021; 13:nu13072149. [PMID: 34201460 PMCID: PMC8308420 DOI: 10.3390/nu13072149] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 06/16/2021] [Accepted: 06/18/2021] [Indexed: 12/12/2022] Open
Abstract
Among the various aspects of health promotion and lifestyle adaptation to the postmenopausal period, nutritional habits are essential because they concern all women, can be modified, and impact both longevity and quality of life. In this narrative review, we discuss the current evidence on the association between dietary patterns and clinical endpoints in postmenopausal women, such as body composition, bone mass, and risk markers for cardiovascular disease. Current evidence suggests that low-fat, plant-based diets are associated with beneficial effects on body composition, but further studies are needed to confirm these results in postmenopausal women. The Mediterranean diet pattern along with other healthy habits may help the primary prevention of bone, metabolic, and cardiovascular diseases in the postmenopausal period. It consists on the use of healthy foods that have anti-inflammatory and antioxidant properties, and is associated with a small but significant decrease in blood pressure, reduction of fat mass, and improvement in cholesterol levels. These effects remain to be evaluated over a longer period of time, with the assessment of hard outcomes such as bone fractures, diabetes, and coronary ischemia.
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Affiliation(s)
- Thais R. Silva
- Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre 90035-003, Brazil;
- Laboratory of Molecular Endocrinology, Department of Physiology, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil
| | - Karen Oppermann
- Medical School of Universidade de Passo Fundo, São Vicente de Paulo Hospital, Passo Fundo 99052-900, Brazil;
| | - Fernando M. Reis
- Division of Human Reproduction, Hospital das Clínicas, Department of Obstetrics and Gynecology, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brazil
- Correspondence: (F.M.R.); (P.M.S.); Tel.: +55-51-3359-8027 (P.M.S.)
| | - Poli Mara Spritzer
- Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre 90035-003, Brazil;
- Laboratory of Molecular Endocrinology, Department of Physiology, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil
- Correspondence: (F.M.R.); (P.M.S.); Tel.: +55-51-3359-8027 (P.M.S.)
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The Dual Role of Vitamin K2 in "Bone-Vascular Crosstalk": Opposite Effects on Bone Loss and Vascular Calcification. Nutrients 2021; 13:nu13041222. [PMID: 33917175 PMCID: PMC8067793 DOI: 10.3390/nu13041222] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 03/30/2021] [Accepted: 04/04/2021] [Indexed: 12/13/2022] Open
Abstract
Osteoporosis (OP) and vascular calcification (VC) represent relevant health problems that frequently coexist in the elderly population. Traditionally, they have been considered independent processes, and mainly age-related. However, an increasing number of studies have reported their possible direct correlation, commonly defined as “bone-vascular crosstalk”. Vitamin K2 (VitK2), a family of several natural isoforms also known as menaquinones (MK), has recently received particular attention for its role in maintaining calcium homeostasis. In particular, VitK2 deficiency seems to be responsible of the so-called “calcium paradox” phenomenon, characterized by low calcium deposition in the bone and its accumulation in the vessel wall. Since these events may have important clinical consequences, and the role of VitK2 in bone-vascular crosstalk has only partially been explained, this review focuses on its effects on the bone and vascular system by providing a more recent literature update. Overall, the findings reported here propose the VitK2 family as natural bioactive molecules that could be able to play an important role in the prevention of bone loss and vascular calcification, thus encouraging further in-depth studies to achieve its use as a dietary food supplement.
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Chang B, Liu X. Osteon: Structure, Turnover, and Regeneration. TISSUE ENGINEERING PART B-REVIEWS 2021; 28:261-278. [PMID: 33487116 DOI: 10.1089/ten.teb.2020.0322] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Bone is composed of dense and solid cortical bone and honeycomb-like trabecular bone. Although cortical bone provides the majority of mechanical strength for a bone, there are few studies focusing on cortical bone repair or regeneration. Osteons (the Haversian system) form structural and functional units of cortical bone. In recent years, emerging evidences have shown that the osteon structure (including osteocytes, lamellae, lacunocanalicular network, and Haversian canals) plays critical roles in bone mechanics and turnover. Therefore, reconstruction of the osteon structure is crucial for cortical bone regeneration. This article provides a systematic summary of recent advances in osteons, including the structure, function, turnover, and regenerative strategies. First, the hierarchical structure of osteons is illustrated and the critical functions of osteons in bone dynamics are introduced. Next, the modeling and remodeling processes of osteons at a cellular level and the turnover of osteons in response to mechanical loading and aging are emphasized. Furthermore, several bioengineering approaches that were recently developed to recapitulate the osteon structure are highlighted. Impact statement This review provides a comprehensive summary of recent advances in osteons, especially the roles in bone formation, remodeling, and regeneration. Besides introducing the hierarchical structure and critical functions of osteons, we elucidate the modeling and remodeling of osteons at a cellular level. Specifically, we highlight the bioengineering approaches that were recently developed to mimic the hierarchical structure of osteons. We expect that this review will provide informative insights and attract increasing attentions in orthopedic community, shedding light on cortical bone regeneration in the future.
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Affiliation(s)
- Bei Chang
- Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, Texas, USA
| | - Xiaohua Liu
- Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, Texas, USA
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Cui Q, Li N, Nie F, Yang F, Li H, Zhang J. Vitamin K2 promotes the osteogenic differentiation of periodontal ligament stem cells via the Wnt/β-catenin signaling pathway. Arch Oral Biol 2021; 124:105057. [PMID: 33517171 DOI: 10.1016/j.archoralbio.2021.105057] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 12/30/2020] [Accepted: 01/05/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Vitamin K2 (MK-4, menaquinone 4) plays an important role in osteoprotection. The present study aimed to examine the effect of MK-4 on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in vitro and probed the potential signaling pathway. DESIGN PDLSCs were isolated from extracted premolars by tissue block culture method and were identified by flow cytometry. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to determine the effect of MK-4 on the proliferation of PDLSCs. Alkaline phosphatase (ALP) activity was analyzed quantitatively, and extracellular matrix mineralization was examined by Alizarin Red S staining. The mRNA and protein expression levels of ALP, Runx Family Transcription Factor 2 (Runx2), osteocalcin (OCN), and Sp7 Transcription Factor (SP7; Osterix) were measured by qRT-PCR and Western blot. In addition, after adding the inhibitor XAV-939, Western blot was used to assess the correlation with the Wnt/β-catenin signaling pathway. The above results were obtained by observing at least three fields randomly, and each experiment was repeated at least three times. RESULTS This study found that 10-5 M MK-4 significantly promoted the osteogenic differentiation of PDLSCs. Gene and protein expression levels of ALP, Runx2, OCN, and Osterix were all upregulated compared with control. Remarkably, after blocking the Wnt/β-catenin signaling pathway with XAV-939, the effect of MK-4 was apparently reversed. CONCLUSION These results demonstrate that MK-4 can promote the osteogenic differentiation of PDLSCs, which is likely related to the activation of the Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Qun Cui
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No. 44-1 Wenhua Road West, 250012, Jinan, Shandong, China.
| | - Na Li
- Stomatology Department of The First Affiliated Hospital of Shandong First Medical University, No. 16766, Jingshi Road, 250012, Jinan, Shandong, China.
| | - Fujiao Nie
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No. 44-1 Wenhua Road West, 250012, Jinan, Shandong, China.
| | - Fan Yang
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No. 44-1 Wenhua Road West, 250012, Jinan, Shandong, China.
| | - Hongkun Li
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No. 44-1 Wenhua Road West, 250012, Jinan, Shandong, China.
| | - Jun Zhang
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No. 44-1 Wenhua Road West, 250012, Jinan, Shandong, China.
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Sylvester FA. Effects of Digestive Diseases on Bone Metabolism. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:1023-1031.e7. [DOI: 10.1016/b978-0-323-67293-1.00091-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Abstract
PURPOSE OF REVIEW Osteoporosis is commonly diagnosed through the clinical assessment of bone quantity using bone mineral density; however, the primary clinical concern is bone fragility. Bone fragility is determined by both bone quantity and bone quality. Over the past decade, the gut microbiome has emerged as a factor that can regulate diseases throughout the body. This review discusses how microbial organisms and their genetic products that inhabit the gastrointestinal tract influence bone quantity, bone quality, and bone strength. RECENT FINDINGS Recent studies have shown that the gut microbiome regulates bone loss during estrogen depletion and glucocorticoid treatment. A series of studies has also shown that the gut microbiome influences whole bone strength by modifying bone tissue quality. The possible links between the gut microbiome and bone tissue quality are discussed focusing on the effects of microbiome-derived vitamin K. We provide a brief introduction to the gut microbiome and how modifications to the gut microbiome may lead to changes in bone. The gut microbiome is a promising target for new therapeutic approaches that address bone quality in ways not possible with current interventions.
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Affiliation(s)
- Macy Castaneda
- Sibley School of Mechanical and Aerospace Engineering, Cornell University, 124 Hoy Road, 355 Upson Hall, Ithaca, NY, 14850, USA
| | - Jasmin M Strong
- Sibley School of Mechanical and Aerospace Engineering, Cornell University, 124 Hoy Road, 355 Upson Hall, Ithaca, NY, 14850, USA
| | - Denise A Alabi
- Sibley School of Mechanical and Aerospace Engineering, Cornell University, 124 Hoy Road, 355 Upson Hall, Ithaca, NY, 14850, USA
| | - Christopher J Hernandez
- Sibley School of Mechanical and Aerospace Engineering, Cornell University, 124 Hoy Road, 355 Upson Hall, Ithaca, NY, 14850, USA.
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Goto S, Setoguchi S, Nagata-Akaho N, Terada K, Watase D, Yamakawa H, Toki E, Koga M, Matsunaga K, Karube Y, Takata J. Ester derivatives of phyllohydroquinone effectively deliver the active form of vitamin K 1 topically, owing to their non-photosensitivity. Eur J Pharm Sci 2020; 155:105519. [PMID: 32822810 DOI: 10.1016/j.ejps.2020.105519] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 08/12/2020] [Accepted: 08/17/2020] [Indexed: 11/28/2022]
Abstract
Topical application of phylloquinone (PK) is beneficial to the skin; however, its topical use is limited in Europe owing to its photosensitive properties such as photodegradation and phototoxicity. We evaluated the suitability of ester derivatives of phyllohydroquinone (PKH), the active form of PK, for topical application to overcome the abovementioned problems of PK. We used the PKH derivatives PKH-1,4-bis-N,N-dimethylglycinate hydrochloride (PKH-DMG) and PKH-1,4-bis-hemisuccinate (PKH-SUC) for our studies. Photostability was determined by measuring the residual concentration after irradiation with artificial sunlight and multi-wavelength light. Phototoxicity after ultraviolet A (UVA) irradiation was assessed by measuring drug-induced singlet oxygen and intracellular reactive oxygen species (ROS) generation, and cell viability of a human epidermal keratinocyte cell line (HaCaT). Delivery of PKH into HaCaT cells was assessed by measuring PK epoxide (PKO) levels. The PKH derivatives showed higher photostability than PK. After UVA irradiation, PK induced high singlet oxygen levels and intracellular ROS generation, and reduced cell viability, whereas the PKH derivatives showed no effects. The PKH derivatives increased intracellular PKO levels. AUCPKO(0-72 h) values after PKH-DMG and PKH-SUC treatments were 0.741- and 22.9-fold higher than that after PK treatment, respectively. In conclusion, PKH derivatives act as PKH prodrugs and are suitable for topical application without the need for special protection from light.
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Affiliation(s)
- Shotaro Goto
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
| | - Shuichi Setoguchi
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
| | - Nami Nagata-Akaho
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
| | - Kazuki Terada
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
| | - Daisuke Watase
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
| | - Hirofumi Yamakawa
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
| | - Erina Toki
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
| | - Mitsuhisa Koga
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
| | | | - Yoshiharu Karube
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
| | - Jiro Takata
- Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
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Beato S, Toledo-Solís FJ, Fernández I. Vitamin K in Vertebrates' Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species. Biomolecules 2020; 10:E1303. [PMID: 32917043 PMCID: PMC7564532 DOI: 10.3390/biom10091303] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/04/2020] [Accepted: 09/04/2020] [Indexed: 12/15/2022] Open
Abstract
Vitamin K (VK) is a fat-soluble vitamin that vertebrates have to acquire from the diet, since they are not able to de novo synthesize it. VK has been historically known to be required for the control of blood coagulation, and more recently, bone development and homeostasis. Our understanding of the VK metabolism and the VK-related molecular pathways has been also increased, and the two main VK-related pathways-the pregnane X receptor (PXR) transactivation and the co-factor role on the γ-glutamyl carboxylation of the VK dependent proteins-have been thoroughly investigated during the last decades. Although several studies evidenced how VK may have a broader VK biological function than previously thought, including the reproduction, little is known about the specific molecular pathways. In vertebrates, sex differentiation and gametogenesis are tightly regulated processes through a highly complex molecular, cellular and tissue crosstalk. Here, VK metabolism and related pathways, as well as how gametogenesis might be impacted by VK nutritional status, will be reviewed. Critical knowledge gaps and future perspectives on how the different VK-related pathways come into play on vertebrate's reproduction will be identified and proposed. The present review will pave the research progress to warrant a successful reproductive status through VK nutritional interventions as well as towards the establishment of reliable biomarkers for determining proper nutritional VK status in vertebrates.
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Affiliation(s)
- Silvia Beato
- Campus de Vegazana, s/n, Universidad de León (ULE), 24071 León, Spain;
| | - Francisco Javier Toledo-Solís
- Consejo Nacional de Ciencia y Tecnología (CONACYT, México), Av. Insurgentes Sur 1582, Col. Crédito Constructor, Alcaldía Benito Juárez, C.P. 03940 Ciudad de Mexico, Mexico;
- Department of Biology and Geology, University of Almería, 04120 Almería, Spain
| | - Ignacio Fernández
- Center for Aquaculture Research, Agrarian Technological Institute of Castile and Leon, Ctra. Arévalo, s/n, 40196 Zamarramala, Segovia, Spain
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Chen L, Shi X, Weng SJ, Xie J, Tang JH, Yan DY, Wang BZ, Xie ZJ, Wu ZY, Yang L. Vitamin K2 Can Rescue the Dexamethasone-Induced Downregulation of Osteoblast Autophagy and Mitophagy Thereby Restoring Osteoblast Function In Vitro and In Vivo. Front Pharmacol 2020; 11:1209. [PMID: 32848799 PMCID: PMC7431688 DOI: 10.3389/fphar.2020.01209] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 07/24/2020] [Indexed: 12/12/2022] Open
Abstract
Chronic long-term glucocorticoids (GC) use is associated with glucocorticoid-induced osteoporosis (GIOP) by inhibiting the survival and impairing the functions of osteoblasts. Autophagy and mitophagy play key roles in osteoblast differentiation, mineralization and survival, and mounting evidence have implicated osteoblast autophagy and mitophagy as a novel mechanism in the pathogenesis of GIOP. Vitamin K2 (VK2) is an essential nutrient supplement that have been shown to exert protective effects against osteoporotic bone loss including GIOP. In this study, we showed that the glucocorticoid dexamethasone (Dex) deregulated osteoblast autophagy and mitophagy by downregulating the expression of autophagic and mitophagic markers LC3-II, PINK1, Parkin. This consequently led to inhibition of osteoblast differentiation and mineralization function in vitro. Interestingly, co-treatment with VK2 significantly attenuated the Dex-induced downregulation of LC3-II, PINK1, Parkin, thereby restoring autophagic and mitophagic processes and normal osteoblastic activity. In addition, using an established rat model of GIOP, we showed that VK2 administration can protect rats against the deleterious effects of Dex on bone by reinstating autophagic and mitophagic activities in bone tissues. Collectively, our results provide new insights into the role of osteoblast autophagy and mitophagy in GIOP. Additionally, the use of VK2 supplementation to augment osteoblast autophagy/mitophagy may significantly improve clinical outcomes of GIOP patients.
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Affiliation(s)
- Liang Chen
- Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, China
| | - Xiang Shi
- School of Mental Health, Wenzhou Medical University, Wenzhou, China
| | - She-Ji Weng
- Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jun Xie
- Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, China
| | - Jia-Hao Tang
- Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, China
| | - De-Yi Yan
- Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, China
| | - Bing-Zhang Wang
- Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, China
| | - Zhong-Jie Xie
- Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zong-Yi Wu
- Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Lei Yang
- Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, China
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Naqvi SM, Panadero Pérez JA, Kumar V, Verbruggen ASK, McNamara LM. A Novel 3D Osteoblast and Osteocyte Model Revealing Changes in Mineralization and Pro-osteoclastogenic Paracrine Signaling During Estrogen Deficiency. Front Bioeng Biotechnol 2020; 8:601. [PMID: 32656194 PMCID: PMC7326002 DOI: 10.3389/fbioe.2020.00601] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 05/18/2020] [Indexed: 11/13/2022] Open
Abstract
Recent in vitro studies have revealed that the mechanobiological responses of osteoblasts and osteocytes are fundamentally impaired during estrogen deficiency. However, these two-dimensional (2D) cell culture studies do not account for in vivo biophysical cues. Thus, the objectives of this study are to (1) develop a three-dimensional (3D) osteoblast and osteocyte model integrated into a bioreactor and (2) apply this model to investigate whether estrogen deficiency leads to changes in osteoblast to osteocyte transition, mechanosensation, mineralization, and paracrine signaling associated with bone resorption by osteoclasts. MC3T3-E1s were expanded in media supplemented with estrogen (17β-estradiol). These cells were encapsulated in gelatin-mtgase before culture in (1) continued estrogen (E) or (2) no further estrogen supplementation. Constructs were placed in gas permeable and water impermeable cell culture bags and maintained at 5% CO2 and 37°C. These bags were either mechanically stimulated in a custom hydrostatic pressure (HP) bioreactor or maintained under static conditions (control). We report that osteocyte differentiation, characterized by the presence of dendrites and staining for osteocyte marker dentin matrix acidic phosphoprotein 1 (DMP1), was significantly greater under estrogen withdrawal (EW) compared to under continuous estrogen treatment (day 21). Mineralization [bone sialoprotein (BSP), osteopontin (OPN), alkaline phosphatase (ALP), calcium] and gene expression associated with paracrine signaling for osteoclastogenesis [receptor activator of nuclear factor kappa-β ligand (RANKL)/osteoprotegerin OPG ratio] were significantly increased in estrogen deficient and mechanically stimulated cells. Interestingly, BSP and DMP-1 were also increased at day 1 and day 21, respectively, which play a role in regulation of biomineralization. Furthermore, the increase in pro-osteoclastogenic signaling may be explained by altered mechanoresponsiveness of osteoblasts or osteocytes during EW. These findings highlight the impact of estrogen deficiency on bone cell function and provide a novel in vitro model to investigate the mechanisms underpinning changes in bone cells after estrogen deficiency.
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Affiliation(s)
| | | | | | | | - Laoise M. McNamara
- Mechanobiology and Medical Device Research Group, Department of Biomedical Engineering, College of Engineering and Informatics, National University of Ireland Galway, Galway, Ireland
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Zhang Y, Liu Z, Duan L, Ji Y, Yang S, Zhang Y, Li H, Wang Y, Wang P, Chen J, Li Y. Effect of Low-Dose Vitamin K2 Supplementation on Bone Mineral Density in Middle-Aged and Elderly Chinese: A Randomized Controlled Study. Calcif Tissue Int 2020; 106:476-485. [PMID: 32060566 DOI: 10.1007/s00223-020-00669-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 02/03/2020] [Indexed: 10/25/2022]
Abstract
Previous studies indicated a positive effect of vitamin K2 (VK2) supplementation on bone turnover biomarkers and bone mineral density (BMD), but the doses varied, and few studies have focused on the difference between VK2 supplementation alone and in combination with calcium and vitamin D3. The aim of this study was to explore a low and effective dose of VK2 for improving BMD, and to examine whether the co-supplementation of VK2, calcium and vitamin D3 would bring greater effects. In this trial, a total of 311 community-dwelling men and postmenopausal women aged 50 and 75 years were randomly assigned to four groups, receiving placebo, 50 µg/day, 90 µg/day or co-supplementation with calcium (500 mg/day) and vitamin D3 (10 µg/day) for 1 year. At the endpoint, the bone loss of femoral neck was significantly lower in postmenopausal women in the two 90 µg groups (treatment × time, p = 0.006) compared with placebo, but no effects in men. Serum biomarkers cOC/ucOC ratio increased in the intervention groups (treatment × time, p < 0.001). VK2 supplementation in dose of 90 µg/day performed a significant effect on reducing bone loss in postmenopausal women, but in combination with calcium and vitamin D3 brought no additional effects.Trial registration This trial was registered at http://www.chictr.org.cn as chiCTR1800019240.
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Affiliation(s)
- Yingfeng Zhang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150086, People's Republic of China
| | - Zhipeng Liu
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150086, People's Republic of China
| | - Lili Duan
- Vitamin K2 Research Center, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110015, People's Republic of China
| | - Yeyu Ji
- Vitamin K2 Research Center, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110015, People's Republic of China
| | - Sen Yang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150086, People's Republic of China
| | - Yuan Zhang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150086, People's Republic of China
| | - Hongyin Li
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150086, People's Republic of China
| | - Yu Wang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150086, People's Republic of China
| | - Peng Wang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150086, People's Republic of China
| | - Jiepeng Chen
- Vitamin K2 Research Center, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110015, People's Republic of China.
| | - Ying Li
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150086, People's Republic of China.
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36
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Sim M, Lewis JR, Prince RL, Levinger I, Brennan-Speranza TC, Palmer C, Bondonno CP, Bondonno NP, Devine A, Ward NC, Byrnes E, Schultz CJ, Woodman R, Croft K, Hodgson JM, Blekkenhorst LC. The effects of vitamin K-rich green leafy vegetables on bone metabolism: A 4-week randomised controlled trial in middle-aged and older individuals. Bone Rep 2020; 12:100274. [PMID: 32455149 PMCID: PMC7235933 DOI: 10.1016/j.bonr.2020.100274] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 04/21/2020] [Indexed: 01/20/2023] Open
Abstract
Background High vegetable intake is associated with beneficial effects on bone. However, the mechanisms remain uncertain. Green leafy vegetables are a rich source of vitamin K1, which is known to have large effects on osteoblasts and osteocalcin (OC) metabolism. Objective To examine the effects of consumption of two to three extra serves of green leafy vegetables daily on bone metabolism. Methods Thirty individuals (mean age 61.8 ± 9.9 years, 67% male) completed three experimental phases in a randomised controlled crossover design, each lasting four weeks, with a washout period of four weeks between phases (clinical trial registration: ACTRN12615000194561). The three experimental phases were: (i) increased dietary vitamin K1 by consuming green leafy vegetables (H-K; ~200 g/d containing 164.3 [99.5-384.7] μg/d of vitamin K1); (ii) low vitamin K1 by consuming vitamin K1-poor vegetables (L-K; ~200 g/d containing 9.4 [7.7-11.6] μg/d of vitamin K1); and (iii) control (CON) where participants consumed an energy-matched non-vegetable control. OC forms, total OC (tOC), carboxylated OC (cOC) and undercarboxylated OC (ucOC), were measured in serum pre- and post-intervention for each experimental phase using a sandwich-electrochemiluminescence immunoassay. Results Pre-intervention tOC, ucOC and ucOC:tOC levels were similar between phases (P > .05). Following H-K, but not L-K, tOC, ucOC and ucOC:tOC levels were significantly lower compared to pre-intervention levels (P ≤ .001) and compared to CON (~14%, 31% and 19%, respectively, all P < .05), while cOC remained unchanged. Conclusions In middle-aged healthy men and women, an easily achieved increase in dietary intake of vitamin K1-rich green leafy vegetables substantially reduces serum tOC and ucOC suggesting increased entry of OC into bone matrix, where it may improve the material property of bone. In conjunction with previous epidemiological and randomised controlled trial data, these findings suggest that interventions to increase vegetable intake over extended periods should include bone end points including fracture risk.
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Key Words
- Ageing
- BMD, bone mineral density
- Bone
- CON, control
- CTX, collagen type I C-terminal cross-linked telopeptide
- FFQ, food frequency questionnaire
- GCMS, gas-chromatography mass spectrometry
- H-K, experimental phase with high vitamin K1 intake
- L-K, experimental phase with low vitamin K1 intake
- METs, metabolic equivalents
- MK, menaquinones
- Nutrition
- OC, osteocalcin
- Osteocalcin
- P1NP, N-terminal propeptide of type I collagen
- PK, phylloquinone
- RCT, randomised controlled trial
- USDA, United States Department of Agriculture
- VIABP, Vegetable intake and blood pressure study
- VKDP, vitamin K dependant proteins
- Vitamin K
- cOC, carboxylated osteocalcin
- tOC, total osteocalcin
- ucOC, undercarboxylated osteocalcin
- ucOC:tOC, fraction of undercarboxylated osteocalcin
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Affiliation(s)
- Marc Sim
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.,Medical School, Royal Perth Hospital Unit, The University Western Australia, Perth, WA, Australia
| | - Joshua R Lewis
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.,Medical School, Royal Perth Hospital Unit, The University Western Australia, Perth, WA, Australia.,Centre for Kidney Research, Children's Hospital at Westmead, School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Richard L Prince
- Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.,Medical School, Sir Charles Gardner Unit, The University Western Australia, Perth, WA, Australia
| | - Itamar Levinger
- Institute for Health and Sport (iHeS), Victoria University, Melbourne, VIC, Australia.,Australian Institute for Musculoskeletal Science (AIMSS), University of Melbourne and Western Health, St Albans, VIC, Australia
| | - Tara C Brennan-Speranza
- Department of Physiology, Bosch Institute for Medical Research, University of Sydney, Sydney, Australia
| | - Claire Palmer
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.,School of Biomedical Science, Royal Perth Hospital Unit, The University Western Australia, Perth, WA, Australia
| | - Catherine P Bondonno
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.,Medical School, Royal Perth Hospital Unit, The University Western Australia, Perth, WA, Australia
| | - Nicola P Bondonno
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.,Medical School, Royal Perth Hospital Unit, The University Western Australia, Perth, WA, Australia
| | - Amanda Devine
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
| | - Natalie C Ward
- Medical School, Royal Perth Hospital Unit, The University Western Australia, Perth, WA, Australia.,School of Public Health & Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia
| | - Elizabeth Byrnes
- Department of Clinical Biochemistry, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, Australia
| | - Carl J Schultz
- Medical School, Royal Perth Hospital Unit, The University Western Australia, Perth, WA, Australia.,Department of Cardiology, Royal Perth Hospital, WA, Australia
| | - Richard Woodman
- Flinders Centre for Epidemiology and Biostatistics, Flinders University, Adelaide, SA, Australia
| | - Kevin Croft
- School of Biomedical Science, Royal Perth Hospital Unit, The University Western Australia, Perth, WA, Australia
| | - Jonathan M Hodgson
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.,Medical School, Royal Perth Hospital Unit, The University Western Australia, Perth, WA, Australia
| | - Lauren C Blekkenhorst
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.,Medical School, Royal Perth Hospital Unit, The University Western Australia, Perth, WA, Australia
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Nasello G, Alamán-Díez P, Schiavi J, Pérez MÁ, McNamara L, García-Aznar JM. Primary Human Osteoblasts Cultured in a 3D Microenvironment Create a Unique Representative Model of Their Differentiation Into Osteocytes. Front Bioeng Biotechnol 2020; 8:336. [PMID: 32391343 PMCID: PMC7193048 DOI: 10.3389/fbioe.2020.00336] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 03/26/2020] [Indexed: 01/12/2023] Open
Abstract
Microengineered systems provide an in vitro strategy to explore the variability of individual patient response to tissue engineering products, since they prefer the use of primary cell sources representing the phenotype variability. Traditional in vitro systems already showed that primary human osteoblasts embedded in a 3D fibrous collagen matrix differentiate into osteocytes under specific conditions. Here, we hypothesized that translating this environment to the organ-on-a-chip scale creates a minimal functional unit to recapitulate osteoblast maturation toward osteocytes and matrix mineralization. Primary human osteoblasts were seeded in a type I collagen hydrogel, to establish the role of lower (2.5 × 105 cells/ml) and higher (1 × 106 cells/ml) cell density on their differentiation into osteocytes. A custom semi-automatic image analysis software was used to extract quantitative data on cellular morphology from brightfield images. The results are showing that cells cultured at a high density increase dendrite length over time, stop proliferating, exhibit dendritic morphology, upregulate alkaline phosphatase (ALP) activity, and express the osteocyte marker dental matrix protein 1 (DMP1). On the contrary, cells cultured at lower density proliferate over time, do not upregulate ALP and express the osteoblast marker bone sialoprotein 2 (BSP2) at all timepoints. Our work reveals that microengineered systems create unique conditions to capture the major aspects of osteoblast differentiation into osteocytes with a limited number of cells. We propose that the microengineered approach is a functional strategy to create a patient-specific bone tissue model and investigate the individual osteogenic potential of the patient bone cells.
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Affiliation(s)
- Gabriele Nasello
- Multiscale in Mechanical and Biological Engineering (M2BE), University of Zaragoza, Zaragoza, Spain.,Biomechanics Section, Department of Mechanical Engineering, KU Leuven, Leuven, Belgium
| | - Pilar Alamán-Díez
- Multiscale in Mechanical and Biological Engineering (M2BE), University of Zaragoza, Zaragoza, Spain
| | - Jessica Schiavi
- Mechanobiology and Medical Device Research Group (MMDRG), National University of Ireland Galway, Galway, Ireland
| | - María Ángeles Pérez
- Multiscale in Mechanical and Biological Engineering (M2BE), University of Zaragoza, Zaragoza, Spain
| | - Laoise McNamara
- Mechanobiology and Medical Device Research Group (MMDRG), National University of Ireland Galway, Galway, Ireland
| | - José Manuel García-Aznar
- Multiscale in Mechanical and Biological Engineering (M2BE), University of Zaragoza, Zaragoza, Spain
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Sarkar N, Bose S. Controlled Delivery of Curcumin and Vitamin K2 from Hydroxyapatite-Coated Titanium Implant for Enhanced in Vitro Chemoprevention, Osteogenesis, and in Vivo Osseointegration. ACS APPLIED MATERIALS & INTERFACES 2020; 12:13644-13656. [PMID: 32013377 PMCID: PMC8015417 DOI: 10.1021/acsami.9b22474] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/02/2023]
Abstract
Successful repair of critical-sized tumor-resection defects, especially in load-bearing bones, still remains a major challenge in clinical orthopedics. Titanium (Ti) implants have been increasingly used in the past few decades because of titanium's suitable mechanical properties and biocompatibility; however, it shows insufficient integration with the surrounding bone. In this study, the plasma spray technique is utilized to form homogeneous hydroxyapatite (HA) coating on the surface of the Ti implant to enhance osseointegration at the tissue-implant interface. These coated implants are loaded with curcumin and vitamin K2 to introduce chemopreventive and osteogenesis ability via controlled release of these biomolecules. The synergistic effect of these two biomolecules showed enhanced in vitro osteoblast (hFOB) cell attachment and proliferation for 11 days. Moreover, these biomolecules showed lower in vitro osteosarcoma (MG-63) cell proliferation after 3, 7, and 11 days. An in vivo study was carried out to evaluate the bone bonded zone in a rat distal femur model at an early wound healing stage of 5 days. Modified Masson Goldner staining of the tissue-implant section showed improved contact between tissue and implant in dual drug-loaded HA-coated Ti implants compared to control implants. This work presents a successful fabrication of a mechanically competent functional Ti implant with the advantages of enhanced in vitro osteoblast proliferation, osteosarcoma inhibition, and in vivo osseointegration, indicating the potential for load-bearing bone-defect repair after tumor resection.
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Affiliation(s)
- Naboneeta Sarkar
- W. M. Keck Biomedical Materials Research Laboratory School of Mechanical and Materials Engineering Washington State University Pullman, Washington 99164, United States
| | - Susmita Bose
- W. M. Keck Biomedical Materials Research Laboratory School of Mechanical and Materials Engineering Washington State University Pullman, Washington 99164, United States
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Pazyar N, Houshmand G, Yaghoobi R, Hemmati AA, Zeineli Z, Ghorbanzadeh B. Wound healing effects of topical Vitamin K: A randomized controlled trial. Indian J Pharmacol 2019; 51:88-92. [PMID: 31142943 PMCID: PMC6533928 DOI: 10.4103/ijp.ijp_183_18] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND: The incidence of acute and chronic wounds has rapidly increased which treatment remains as health problem. Previously, we reported the healing effect of Vitamin K in experimental animal models. The aim of this study was to investigate the effects of topical Vitamin K on skin wound healing process in patients. MATERIALS AND METHODS: Sixty-three patients with indication for high-frequency electrocautery were enrolled in this randomized controlled trial. The patients were divided randomly into three groups. All the patients underwent high-frequency electrocautery treatment. Then, the patients in the A group received 1% Vitamin K cream, the patients in the B group received 1% phenytoin cream. Furthermore, the patients in the control group received Eucerin. The wound status (width and the time of recovery) and complications in the three groups were evaluated 2 weeks after procedure by a dermatologist. RESULTS: The effects produced by the topical Vitamin K showed a significant (P < 0.05) healing when compared with Eucerin group in parameters such as wound contraction and time to full recovery. Moreover, the healing time did not differ between phenytoin and Vitamin K groups (P = 0.16). CONCLUSION: A randomized, controlled trial suggests that topical application of Vitamin K significantly reduces healing time in patients.
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Affiliation(s)
- Nader Pazyar
- Department of Dermatology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Gholamreza Houshmand
- Department of Pharmacology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Reza Yaghoobi
- Department of Dermatology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Asghar Hemmati
- Department of Pharmacology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Zahra Zeineli
- Department of Dermatology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Behnam Ghorbanzadeh
- Department of Pharmacology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran
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40
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Ciubean AD, Ungur RA, Irsay L, Ciortea VM, Borda IM, Dogaru GB, Trifa AP, Vesa SC, Buzoianu AD. Polymorphisms of FDPS, LRP5, SOST and VKORC1 genes and their relation with osteoporosis in postmenopausal Romanian women. PLoS One 2019; 14:e0225776. [PMID: 31774873 PMCID: PMC6880991 DOI: 10.1371/journal.pone.0225776] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 11/12/2019] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES This study aimed to assess the relationship between bone mineral density and genotypes of four polymorphisms in previously detected osteoporosis-candidate genes (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438) in postmenopausal Romanian women with primary osteoporosis. METHODS An analytical, prospective, transversal, observational, case-control study on 364 postmenopausal Romanian women was carried out between June 2016 and August 2017 in Cluj Napoca, Romania. Clinical data and blood samples were collected from all study participants. Four polymorphisms were genotyped using TaqMan SNP Genotyping assays, run on a QuantStudio 3 real-time PCR machine. RESULTS Women with TT genotype in FDPS rs2297480 had significantly lower bone mineral density values in the lumbar spine and total hip, and the presence of the T allele was significantly associated with the osteoporosis. Women carrying the CC genotype in LRP5 rs3736228 tend to have lower bone mineral density values in the femoral neck and total hip. No significant association was found for the genotypes of SOST rs1234612 or VKORC1 rs9934438. CONCLUSIONS Our study showed a strong association between bone mineral density and polymorphisms in the FDPS gene, and a borderline association with LRP5 and SOST polymorphisms in postmenopausal Romanian women with osteoporosis. No association was found for VKORC1.
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Affiliation(s)
- Alina Deniza Ciubean
- Department of Rehabilitation, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania
| | - Rodica Ana Ungur
- Department of Rehabilitation, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania
- * E-mail: (RAU); (LI)
| | - Laszlo Irsay
- Department of Rehabilitation, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania
- * E-mail: (RAU); (LI)
| | - Viorela Mihaela Ciortea
- Department of Rehabilitation, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania
| | - Ileana Monica Borda
- Department of Rehabilitation, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania
| | - Gabriela Bombonica Dogaru
- Department of Rehabilitation, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania
| | - Adrian Pavel Trifa
- Department of Genetics, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania
| | - Stefan Cristian Vesa
- Department of Pharmacology, Toxicology and Clinical Pharmacology, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania
| | - Anca Dana Buzoianu
- Department of Pharmacology, Toxicology and Clinical Pharmacology, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania
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Granadeiro L, Dirks RP, Ortiz-Delgado JB, Gavaia PJ, Sarasquete C, Laizé V, Cancela ML, Fernández I. Warfarin-exposed zebrafish embryos resembles human warfarin embryopathy in a dose and developmental-time dependent manner - From molecular mechanisms to environmental concerns. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2019; 181:559-571. [PMID: 31238190 DOI: 10.1016/j.ecoenv.2019.06.042] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 06/13/2019] [Accepted: 06/14/2019] [Indexed: 06/09/2023]
Abstract
Warfarin is the most worldwide used anticoagulant drug and rodenticide. Since it crosses placental barrier it can induce warfarin embryopathy (WE), a fetal mortality in neonates characterized by skeletal deformities in addition to brain hemorrhages. Although the effects of warfarin exposure in aquatic off target species were already described, the particular molecular toxicological mechanisms during early development are still unclear. Here, we used zebrafish (Danio rerio) to describe and compare the developmental effects of warfarin exposure (0, 15.13, 75.68 and 378.43 mM) on two distinct early developmental phases (embryos and eleuthero-embryos). Although exposure to both developmental phases induced fish mortality, only embryos exposed to the highest warfarin level exhibited features mimicking mammalian WE, e.g. high mortality, higher incidence of hemorrhages and altered skeletal development, among other effects. To gain insights into the toxic mechanisms underlying warfarin exposure, the transcriptome of embryos exposed to warfarin was explored through RNA-Seq and compared to that of control embryos. 766 differentially expressed (564 up- and 202 down-regulated) genes were identified. Gene Ontology analysis revealed particular cellular components (cytoplasm, extracellular matrix, lysosome and vacuole), biological processes (mainly amino acid and lipid metabolism and response to stimulus) and pathways (oxidative stress response and apoptosis signaling pathways) being significantly overrepresented in zebrafish embryos upon warfarin exposure. Protein-protein interaction further evidenced an altered redox system, blood coagulation and vasculogenesis, visual phototransduction and collagen formation upon warfarin exposure. The present study not only describes for the first time the WE in zebrafish, it provides new insights for a better risk assessment, and highlights the need for programming the rat eradication actions outside the fish spawning season to avoid an impact on off target fish community. The urge for the development of more species-specific anticoagulants for rodent pest control is also highlighted.
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Affiliation(s)
- Luis Granadeiro
- Centro de Ciências do Mar (CCMAR), Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal
| | - Ron P Dirks
- ZF-screens B.V. J.H. Oortweg 19, 2333, CH Leiden, the Netherlands
| | - Juan B Ortiz-Delgado
- Instituto de Ciencias Marinas de Andalucía-ICMAN/CSIC, Campus Universitario Río San Pedro, Apdo. Oficial, 11510, Puerto Real, Cádiz, Spain
| | - Paulo J Gavaia
- Centro de Ciências do Mar (CCMAR), Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal; Departamento de Ciências Biomédicas e Medicina (DCBM), Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal
| | - Carmen Sarasquete
- Instituto de Ciencias Marinas de Andalucía-ICMAN/CSIC, Campus Universitario Río San Pedro, Apdo. Oficial, 11510, Puerto Real, Cádiz, Spain
| | - Vincent Laizé
- Centro de Ciências do Mar (CCMAR), Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal
| | - M Leonor Cancela
- Centro de Ciências do Mar (CCMAR), Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal; Departamento de Ciências Biomédicas e Medicina (DCBM), Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal; Algarve Biomedical Center (ABC) and Centre for Biomedical Research (CBMR), Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal
| | - Ignacio Fernández
- Centro de Ciências do Mar (CCMAR), Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal; Center for Aquaculture Research, Agrarian Technological Institute of Castile and Leon, Ctra. Arévalo, S/n. 40196 Zamarramala, Segovia, Spain.
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Human osteocyte expression of Nerve Growth Factor: The effect of Pentosan Polysulphate Sodium (PPS) and implications for pain associated with knee osteoarthritis. PLoS One 2019; 14:e0222602. [PMID: 31557169 PMCID: PMC6762051 DOI: 10.1371/journal.pone.0222602] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 09/03/2019] [Indexed: 01/05/2023] Open
Abstract
Pentosan polysulphate sodium (PPS) is a promising therapeutic agent for blocking knee pain in individuals with knee osteoarthritis (KOA). The mode of action of PPS in this context is unknown. We hypothesised that the osteocyte, being the principal cell type in the sub-chondral bone, was capable of expressing the pain mediator Nerve Growth Factor (NGF), and that this may be altered in the presence of PPS. We tested the expression of NGF and the response to PPS in the presence or absence of the proinflammatory cytokine tumour necrosis factor-alpha (TNFα), in human osteocytes. For this we differentiated human primary osteoblasts grown from subchondral bone obtained at primary knee arthroplasty for KOA to an osteocyte-like stage over 28d. We also tested NGF expression in fresh osteocytes obtained by sequential digestion from KOA bone and by immunofluorescence in KOA bone sections. We demonstrate for the first time the production and secretion of NGF/proNGF by this cell type derived from patients with KOA, implicating osteocytes in the pain response in this pathological condition and possibly others. PPS inhibited TNFα-induced levels of proNGF secretion and TNFα induced NGF mRNA expression. Together, this provides evidence that PPS may act to suppress the release of NGF in the subchondral bone to ameliorate pain associated with knee osteoarthritis.
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Abstract
PURPOSE OF REVIEW Osteocytes are responsible for mechanosensing and mechanotransduction in bone and play a crucial role in bone homeostasis. They are embedded in a calcified collagenous matrix and connected with each other through the lacuno-canalicular network. Due to this specific native environment, it is a challenge to isolate primary osteocytes without losing their specific characteristics in vitro. This review summarizes the commonly used and recently established models to study the function of osteocytes in vitro. RECENT FINDINGS Osteocytes are mostly studied in monolayer culture, but recently, 3D models of osteocyte-like cells and primary osteocytes in vitro have been established as well. These models mimic the native environment of osteocytes and show superior osteocyte morphology and behavior, enabling the development of human disease models. Osteocyte-like cell lines as well as primary osteocytes isolated from bone are widely used to study the role of osteocytes in bone homeostasis. Both cells lines and primary cells are cultured in 2D-monolayer and 3D-models. The use of these models and their advantages and shortcomings are discussed in this review.
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Affiliation(s)
- Chen Zhang
- Department of Oral Cell Biology, Amsterdam Movement Sciences, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Department of Clinical Chemistry, Amsterdam Movement Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Astrid D Bakker
- Department of Oral Cell Biology, Amsterdam Movement Sciences, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Jenneke Klein-Nulend
- Department of Oral Cell Biology, Amsterdam Movement Sciences, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Nathalie Bravenboer
- Department of Clinical Chemistry, Amsterdam Movement Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- Department of Internal Medicine, Division of Endocrinology and Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands.
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A comparatively study of menaquinone-7 isolated from Cheonggukjang with vitamin K 1 and menaquinone-4 on osteoblastic cells differentiation and mineralization. Food Chem Toxicol 2019; 131:110540. [PMID: 31173816 DOI: 10.1016/j.fct.2019.05.048] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 05/13/2019] [Accepted: 05/27/2019] [Indexed: 12/25/2022]
Abstract
The effect of menaquinone-7 isolated from cheonggukjang was comparatively investigated with vitamin K1 and menaquinone-4 on cell differentiation and mineralization of the osteoblastic cell line MC3T3-E1. Results indicated that all vitamin K species significantly increased MC3T3-E1 cell proliferation, cellular alkaline phosphatase activity, osteocalcin synthesis, and calcium deposition in a dose-dependent manner. Menaquinone-4 and menaquinone-7 had more potent effects on calcium deposition than vitamin K1, and their effects were only partly reduced by warfarin (γ-carboxylation inhibitor) treatment, while warfarin abolished the induction activity of vitamin K1 on calcification. This suggests that vitamin K1 and K2 (menaquinone-4 & menaquinone-7) may have different mechanisms in stimulating osteoblast mineralization. In addition, the mRNA expression ratio of osteoprotegerin and the receptor activator of nuclear factor-kB ligand was also dramatically increased by treatment with vitamin K1 (62%), menaquinone-4 (247%), and menaquinone-7 (329%), suggesting that vitamin K may suppress the formation of osteoclast by up-regulating the ratio of osteoprotegerin/receptor activator of nuclear factor-kB ligand in osteoblasts. These results provide compelling evidence that vitamin K1, menaquinone-4, and menaquinone-7 all can promote bone health, which might be associated with elevations in the osteoprotegerin/receptor activator of nuclear factor-kB ligand ratio.
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Beneficial Effects of Vitamins K and D3 on Redox Balance of Human Osteoblasts Cultured with Hydroxyapatite-Based Biomaterials. Cells 2019; 8:cells8040325. [PMID: 30965604 PMCID: PMC6523281 DOI: 10.3390/cells8040325] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 04/03/2019] [Accepted: 04/05/2019] [Indexed: 02/07/2023] Open
Abstract
Hydroxyapatite-based biomaterials are commonly used in surgery to repair bone damage. However, the introduction of biomaterials into the body can cause metabolic alterations, including redox imbalance. Because vitamins D3 and K (K1, MK-4, MK-7) have pronounced osteoinductive, anti-inflammatory, and antioxidant properties, it is suggested that they may reduce the adverse effects of biomaterials. The aim of this study was to investigate the effects of vitamins D3 and K, used alone and in combination, on the redox metabolism of human osteoblasts (hFOB 1.19 cell line) cultured in the presence of hydroxyapatite-based biomaterials (Maxgraft, Cerabone, Apatos, and Gen-Os). Culturing of the osteoblasts in the presence of hydroxyapatite-based biomaterials resulted in oxidative stress manifested by increased production of reactive oxygen species and decrease of glutathione level and glutathione peroxidase activity. Such redox imbalance leads to lipid peroxidation manifested by an increase of 4-hydroxynonenal level, which is known to influence the growth of bone cells. Vitamins D3 and K were shown to help maintain redox balance and prevent lipid peroxidation in osteoblasts cultured with hydroxyapatite-based biomaterials. The strongest effect was observed for the combination of vitamin D3 and MK-7. Moreover, vitamins promoted growth of the osteoblasts, manifested by increased DNA biosynthesis. Therefore, it is suggested that the use of vitamins D3 and K may protect redox balance and support the growth of osteoblasts affected by hydroxyapatite-based biomaterials.
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Li W, Zhang S, Liu J, Liu Y, Liang Q. Vitamin K2 stimulates MC3T3‑E1 osteoblast differentiation and mineralization through autophagy induction. Mol Med Rep 2019; 19:3676-3684. [PMID: 30896842 PMCID: PMC6472126 DOI: 10.3892/mmr.2019.10040] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2018] [Accepted: 03/06/2019] [Indexed: 01/02/2023] Open
Abstract
Vitamin K2 likely exerts its protective effects during osteoporosis by promoting osteoblast differentiation and mineralization. However, the precise mechanism remains to be fully elucidated. Autophagy maintains cell homeostasis by breaking down and eliminating damaged proteins and organelles. Increasing evidence in recent years has implicated autophagy in the development of osteoporosis. The aim of the present study was to verify whether vitamin K2 (VK2) can induce autophagy during the differentiation and mineralization of osteoblasts. In the present study, MC3T3-E1 osteoblasts were treated with various doses of VK2 (10−8−10−3 M) for 1–5 days. The results revealed no cytotoxicity at concentrations below 10−5 M, but cell viability was reduced in a dose-dependent manner at concentrations above 10−5 M. Furthermore, MC3T3-E1 osteoblasts were seeded in 6-well plates in complete medium supplemented with dexamethasone, β-glycerophosphate and vitamin C (VC) for osteogenic differentiation. MC3T3-E1 osteoblasts treated with different concentrations (10−5, 10−6 and 10−7 M) of VK2 for 24 h on days 1, 3, 5 and 7 of the differentiation protocol. It was confirmed that VK2 promoted osteoblast differentiation and mineralization by using alkaline phosphatase (ALP) and alizarin red staining. Using western blotting, immunofluorescence, monodansylcadaverine staining and reverse transcription-quantitative polymerase chain reaction, it was observed that VK2 induced autophagy in osteoblasts. The results revealed that VK2 (1 µM) significantly increased ALP activity and the conversion of microtubule associated protein 1 light chain 3-α (LC3)II to LC3I in MC3T3-E1 osteoblasts (P<0.05) at every time point. The number of fluorescent bodies and the intensity increased with VK2, and decreased following treatment with 3-MA+VK2. There was an increase in the mRNA expression levels of ALP, osteocalcin (OCN) and Runt-related transcription factor 2 in VK2-treated cells (P<0.01). The present study further confirmed the association between autophagy and osteoblast differentiation and mineralization through treatment with an autophagy inhibitor [3-methyladenine (3-MA)]. Osteoblasts treated with 3-MA exhibited significant inhibition of ALP activity and osteogenic differentiation (both P<0.05). In addition, ALP activity and osteogenesis in the VK2+3-MA group was lower compared with VK2-treated cells (P<0.05 for both). The present study confirmed that VK2 stimulated autophagy in MC3T3 cells to promote differentiation and mineralization, which may be a potential therapeutic target for osteoporosis.
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Affiliation(s)
- Weiwei Li
- Department of Orthopedics, The First Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China
| | - Shaokun Zhang
- Department of Orthopedics, The First Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China
| | - Jie Liu
- Science Experiment Center of China Medical University, Shenyang, Liaoning 110122, P.R. China
| | - Yongyi Liu
- Department of Orthopedics, The First Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China
| | - Qingwei Liang
- Department of Sports Medicine, The First Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China
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Weng SJ, Xie ZJ, Wu ZY, Yan DY, Tang JH, Shen ZJ, Li H, Bai BL, Boodhun V, Eric Dong XD, Yang L. Effects of combined menaquinone-4 and PTH 1-34 treatment on osetogenesis and angiogenesis in calvarial defect in osteopenic rats. Endocrine 2019; 63:376-384. [PMID: 30244350 DOI: 10.1007/s12020-018-1761-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Accepted: 09/11/2018] [Indexed: 12/19/2022]
Abstract
PURPOSE The aim of this study was to evaluate the effect of combining human parathyroid hormone (1-34) (PTH1-34; PTH) and menaquinone-4 (MK-4) on calvarial bone defect repair in osteopenic rats. METHODS Fourteen week olds were subject to craniotomy for the establishment of osteopenic animal models fed through a chronically low-protein diet. After that, critical calvarial defect model was established and all rats were randomly divided into four groups: sham, MK-4, PTH, and PTH + MK-4. The animals received MK-4 (30 mg/kg/day), PTH1-34 (60 μg/kg, three times a week), or PTH1-34 (60 μg/kg, three times a week) plus MK-4 (30 mg/kg/day) for 8 weeks, respectively. Serum γ-carboxylated osteocalcin (Gla-OC) levels, histological and immunofluorescent labeling were employed to evaluate the bone formation and mineralization in calvarial bone defect. In addition, Microfil perfusion, immunohistochemical, and micro-CT suggested enhanced angiogenesis and bone formation in calvarial bone healing. RESULTS In this study, treatment with either PTH1-34 or MK-4 promoted bone formation and vascular formation in calvarial bone defects compared with the sham group. In addition, combined treatment of PTH1-34 plus MK-4 increased serum level of Gla-OC, improved vascular number and vascular density, and enhanced bone formation in calvarial bone defect in osteopenic conditions as compared with monotherapy. CONCLUSIONS In summary, this study indicated that PTH1-34 plus MK-4 combination therapy accelerated bone formation and angiogenesis in calvarial bone defects in presence of osteopenia.
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MESH Headings
- Animals
- Bone Diseases, Metabolic/complications
- Bone Diseases, Metabolic/diagnosis
- Bone Diseases, Metabolic/drug therapy
- Bone Diseases, Metabolic/pathology
- Drug Therapy, Combination
- Female
- Fracture Healing/drug effects
- Fractures, Spontaneous/diagnosis
- Fractures, Spontaneous/drug therapy
- Fractures, Spontaneous/etiology
- Fractures, Spontaneous/pathology
- Neovascularization, Physiologic/drug effects
- Osteogenesis/drug effects
- Parathyroid Hormone/administration & dosage
- Rats
- Rats, Sprague-Dawley
- Skull/diagnostic imaging
- Skull/drug effects
- Skull/injuries
- Skull/pathology
- Skull Fractures/diagnosis
- Skull Fractures/drug therapy
- Skull Fractures/etiology
- Skull Fractures/pathology
- Vitamin K 2/administration & dosage
- Vitamin K 2/analogs & derivatives
- X-Ray Microtomography
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Affiliation(s)
- She-Ji Weng
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhong-Jie Xie
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zong-Yi Wu
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - De-Yi Yan
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jia-Hao Tang
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zi-Jian Shen
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Hang Li
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Bing-Li Bai
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Viraj Boodhun
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiang Da Eric Dong
- Department of Surgery, Westchester Medical Center / New York Medical College, Valhalla, NY, USA
| | - Lei Yang
- Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
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Silva TRD, Martins CC, Ferreira LL, Spritzer PM. Mediterranean diet is associated with bone mineral density and muscle mass in postmenopausal women. Climacteric 2019; 22:162-168. [PMID: 30661407 DOI: 10.1080/13697137.2018.1529747] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE This study aimed to investigate the association between the Mediterranean diet (MD), body composition, and bone mineral density (BMD) in postmenopausal women. METHODS In this cross-sectional study, 105 apparently healthy postmenopausal women aged between 45 and 65 years were included. BMD, percentage body fat, and appendicular lean mass index (ALMI, appendicular lean mass/height squared) were assessed by dual-energy X-ray absorptiometry. Dietary intake was assessed by a validated food frequency questionnaire. Assessment of MD adherence was based on intake of cereals, vegetables, fruits, meats, dairy products, fish, red wine, and olive oil, and expressed as the Mediterranean diet score (MDS). RESULTS Women with higher adherence to the MD had higher ALMI (6.6 ± 0.8 kg/m2 vs. 6.3 ± 0.7 kg/m2; p = 0.039) and lumbar spine BMD (1.076 ± 0.149 vs. 0.997 ± 0.143 g/cm2; p = 0.007) compared to those with lower MDS. Linear regression analysis adjusted for previous hormone therapy, previous smoking behavior, and habitual physical activity showed an independent positive contribution of MDS to lumbar spine BMD (mean difference 0.088 g/cm2, 95% confidence interval 0.028-0.147; p = 0.004) and ALMI (mean difference 0.296 kg/m2, 95% confidence interval 0.020-0.591; p = 0.049). CONCLUSION Bone mineral density at the lumbar spine and ALMI were positively associated with the MDS in a sample of postmenopausal women from a non-Mediterranean region.
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Affiliation(s)
- T R da Silva
- a Gynecological Endocrinology Unit, Division of Endocrinology , Hospital de Clínicas de Porto Alegre (HCPA) , Porto Alegre , Brazil.,b Post-graduate Program in Endocrinology and Metabolism , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil
| | - C C Martins
- a Gynecological Endocrinology Unit, Division of Endocrinology , Hospital de Clínicas de Porto Alegre (HCPA) , Porto Alegre , Brazil
| | - L L Ferreira
- a Gynecological Endocrinology Unit, Division of Endocrinology , Hospital de Clínicas de Porto Alegre (HCPA) , Porto Alegre , Brazil.,b Post-graduate Program in Endocrinology and Metabolism , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil
| | - P M Spritzer
- a Gynecological Endocrinology Unit, Division of Endocrinology , Hospital de Clínicas de Porto Alegre (HCPA) , Porto Alegre , Brazil.,b Post-graduate Program in Endocrinology and Metabolism , Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.,c Laboratory of Molecular Endocrinology, Department of Physiology , Universidade Federal do Rio Grande do Sul (UFRGS) , Porto Alegre , Brazil
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Combined treatment with vitamin K2 and PTH enhanced bone formation in ovariectomized rats and increased differentiation of osteoblast in vitro. Chem Biol Interact 2019; 300:101-110. [PMID: 30639440 DOI: 10.1016/j.cbi.2019.01.012] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 12/22/2018] [Accepted: 01/09/2019] [Indexed: 02/06/2023]
Abstract
Osteoporosis is accompanied by insufficient osteogenic capacity. Several lines of evidence suggested that solutions to enhance osteoblastogenesis were important strategies for osteoporotic bone defect repair. This study investigated the effect of combined treatment with vitamin K2 and PTH on bone formation in calvarial bone defect in osteoporotic rats and its influence on osteoblast in vitro. Bilateral ovariectomy was used in SPF Sprague Dawley rats to generate an osteoporosis model. Subsequently, a calvarial defect model was established and all osteoporotic rats were randomly assigned to the following groups: control, VK (vitamin K2, 30 mg/kg everyday), PTH (recombinant human PTH (1-34), 60 μg/kg, three times a week) or VK + PTH (vitamin K2, 30 mg/kg everyday plus PTH, 60 μg/kg three times a week) for 8 weeks. In vitro, bone marrow-derived stem cells (BMSCs) were cultured and treated with vitamin K2, PTH or vitamin K2+PTH. ALP staining and western blot were performed to observe the influence of combined treatment on BMSCs. Bone formation within calvarial defect were assessed by serum γ-carboxylated osteocalcin (Gla-OC), micro-CT, histological and immunofluorescent labeling. In this study, combined treatment of PTH and vitamin K2 showed positive effects on preventing bone loss in femurs in OVX rats. Combined treatment increased serum Gla-OC and promoted bone formation in osteoporotic calvarial bone defects. Immunohistochemistry showed that OCN and RUNX2 were more highly expressed in the VK + PTH group than in the control groups. In vitro studies results suggested that combined treatment with PTH and vitamin K2 increased expression of ALP, BMP2 and RUNX2 in BMSCs. Our data suggested that the combination of vitamin K2 and PTH increased differentiation of osteoblast and had a synergistic effect on bone formation in osteoporotic calvarial bone defect.
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