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Miletić M, Stević Z, Perić S, Tančić Gajić M, Rakočević J, Stojanović M, Marković B, Žarković M. Adiponectin and Leptin-Considerations in Adult Patients with Spinal Muscular Atrophy Type 3. Diagnostics (Basel) 2025; 15:529. [PMID: 40075777 PMCID: PMC11899018 DOI: 10.3390/diagnostics15050529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 02/13/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Background: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder characterized by the degeneration of alpha motor neurons in the spinal cord, leading to progressive proximal muscle weakness and paralysis. SMA is clinically categorized into four phenotypes based on age of onset and motor function achieved. Patients with SMA type 3 (juvenile, Kugelberg-Welander disease) initially have the ability to walk unaided, but experience a gradual decline in motor abilities over time. However, their lifespan is not affected by the presence of the disease. Leptin, a cytokine-like hormone secreted by adipocytes, has receptors widely distributed in musculoskeletal tissues. Several studies suggest that adiponectin deficiency contributes to the development of insulin resistance, with lower adiponectin levels closely associated with greater insulin resistance and hyperinsulinemia. However, the role of adiponectin in different types of sarcopenia and its connection to insulin sensitivity remains controversial. The purpose of this study was to measure leptin and adiponectin levels in patients with SMA type 3 and explore their association with markers of insulin sensitivity. Methods: This cross-sectional study included 23 adult patients with SMA type 3 (SMA group) and 18 community-based healthy volunteers (control group), conducted from July 2020 to September 2024. Anthropometric parameters, body composition, body fat percentage, surrogate markers of insulin sensitivity (Homeostasis model assessment of insulin resistance index-HOMA-IR and ISI Matsuda), and circulating levels of leptin and adiponectin were measured in all participants. Results: Insulin resistance was present in 91.3% of patients with SMA type 3, as determined by HOMA-IR and ISI Matsuda insulin sensitivity markers. In the control group, 64.7% had insulin resistance (IR) according to HOMA-IR, while 44.4% met the ISI Matsuda criterion for IR, showing a significant difference in peripheral insulin sensitivity between groups. A significant difference in serum adiponectin levels was observed between patients with SMA type 3 and the control group, whereas there was no significant difference in serum leptin concentrations. High adiponectin levels were observed in 50% of patients with SMA type 3. In the healthy control group, adiponectin levels positively correlated with ISI Matsuda and negatively correlated with HOMA-IR, confirming the insulin-sensitizing role of adiponectin. However, this correlation was not observed in patients with SMA type 3. Conclusions: Our results suggest that in this specific type of hereditary neuromuscular disease, the interplay between sarcopenia and insulin leads to adiponectin resistance, challenging the canonical narrative between insulin sensitivity and adiponectin, and indicating a need for further research.
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Affiliation(s)
- Marija Miletić
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (M.T.G.); (M.S.); (B.M.); (M.Ž.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
| | - Zorica Stević
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
- Clinic of Neurology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Stojan Perić
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
- Clinic of Neurology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Milina Tančić Gajić
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (M.T.G.); (M.S.); (B.M.); (M.Ž.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
| | - Jelena Rakočević
- Institute of Histology and Embryology “Aleksandar Ð. Kostić”, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | - Miloš Stojanović
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (M.T.G.); (M.S.); (B.M.); (M.Ž.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
| | - Bojan Marković
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (M.T.G.); (M.S.); (B.M.); (M.Ž.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
| | - Miloš Žarković
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (M.T.G.); (M.S.); (B.M.); (M.Ž.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
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Wang T, Ye J, Zhang Y, Li J, Yang T, Wang Y, Jiang X, Yao Q. Role of oxytocin in bone. Front Endocrinol (Lausanne) 2024; 15:1450007. [PMID: 39290327 PMCID: PMC11405241 DOI: 10.3389/fendo.2024.1450007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 08/16/2024] [Indexed: 09/19/2024] Open
Abstract
Oxytocin (OT) is a posterior pituitary hormone that, in addition to its role in regulating childbirth and lactation, also exerts direct regulatory effects on the skeleton through peripheral OT and oxytocin receptor (OTR). Bone marrow mesenchymal stem cells (BMSCs), osteoblasts (OB), osteoclasts (OC), chondrocytes, and adipocytes all express OT and OTR. OT upregulates RUNX2, BMP2, ALP, and OCN, thereby enhancing the activity of BMSCs and promoting their differentiation towards OB rather than adipocytes. OT also directly regulates OPG/RANKL to inhibit adipocyte generation, increase the expression of SOX9 and COMP, and enhance chondrocyte differentiation. OB can secrete OT, exerting influence on the surrounding environment through autocrine and paracrine mechanisms. OT directly increases OC formation through the NκB/MAP kinase signaling pathway, inhibits osteoclast proliferation by triggering cytoplasmic Ca2+ release and nitric oxide synthesis, and has a dual regulatory effect on OCs. Under the stimulation of estrogen, OB synthesizes OT, amplifying the biological effects of estrogen and OT. Mediated by estrogen, the OT/OTR forms a feedforward loop with OB. Apart from estrogen, OT also interacts with arginine vasopressin (AVP), prostaglandins (PGE2), leptin, and adiponectin to regulate bone metabolism. This review summarizes recent research on the regulation of bone metabolism by OT and OTR, aiming to provide insights into their clinical applications and further research.
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Affiliation(s)
- Tianming Wang
- Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jianya Ye
- Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- Department of Orthopedic Surgery, Huaian Hospital of Huaian City, Huaian, China
| | - Yongqiang Zhang
- Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jiayi Li
- Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Tianxiao Yang
- Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yufeng Wang
- Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xiao Jiang
- Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Qingqiang Yao
- Department of Orthopedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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Maisenbacher TC, Ehnert S, Histing T, Nüssler AK, Menger MM. Advantages and Limitations of Diabetic Bone Healing in Mouse Models: A Narrative Review. Biomedicines 2023; 11:3302. [PMID: 38137522 PMCID: PMC10741210 DOI: 10.3390/biomedicines11123302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/29/2023] [Accepted: 12/09/2023] [Indexed: 12/24/2023] Open
Abstract
Diabetes represents a major risk factor for impaired fracture healing. Type 2 diabetes mellitus is a growing epidemic worldwide, hence an increase in diabetes-related complications in fracture healing can be expected. However, the underlying mechanisms are not yet completely understood. Different mouse models are used in preclinical trauma research for fracture healing under diabetic conditions. The present review elucidates and evaluates the characteristics of state-of-the-art murine diabetic fracture healing models. Three major categories of murine models were identified: Streptozotocin-induced diabetes models, diet-induced diabetes models, and transgenic diabetes models. They all have specific advantages and limitations and affect bone physiology and fracture healing differently. The studies differed widely in their diabetic and fracture healing models and the chosen models were evaluated and discussed, raising concerns in the comparability of the current literature. Researchers should be aware of the presented advantages and limitations when choosing a murine diabetes model. Given the rapid increase in type II diabetics worldwide, our review found that there are a lack of models that sufficiently mimic the development of type II diabetes in adult patients over the years. We suggest that a model with a high-fat diet that accounts for 60% of the daily calorie intake over a period of at least 12 weeks provides the most accurate representation.
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Affiliation(s)
- Tanja C. Maisenbacher
- Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tübingen, BG Clinic Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany; (T.H.); (M.M.M.)
- Siegfried Weller Institute at the BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany; (S.E.); (A.K.N.)
| | - Sabrina Ehnert
- Siegfried Weller Institute at the BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany; (S.E.); (A.K.N.)
| | - Tina Histing
- Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tübingen, BG Clinic Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany; (T.H.); (M.M.M.)
| | - Andreas K. Nüssler
- Siegfried Weller Institute at the BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany; (S.E.); (A.K.N.)
| | - Maximilian M. Menger
- Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tübingen, BG Clinic Tübingen, Schnarrenbergstr. 95, D-72076 Tübingen, Germany; (T.H.); (M.M.M.)
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Deepika F, Bathina S, Armamento-Villareal R. Novel Adipokines and Their Role in Bone Metabolism: A Narrative Review. Biomedicines 2023; 11:644. [PMID: 36831180 PMCID: PMC9953715 DOI: 10.3390/biomedicines11020644] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 02/02/2023] [Accepted: 02/14/2023] [Indexed: 02/23/2023] Open
Abstract
The growing burden of obesity and osteoporosis is a major public health concern. Emerging evidence of the role of adipokines on bone metabolism has led to the discovery of novel adipokines over the last decade. Obesity is recognized as a state of adipose tissue inflammation that adversely affects bone health. Adipokines secreted from white adipose tissue (WAT) and bone marrow adipose tissue (BMAT) exerts endocrine and paracrine effects on the survival and function of osteoblasts and osteoclasts. An increase in marrow fat is implicated in osteoporosis and, hence, it is crucial to understand the complex interplay between adipocytes and bone. The objective of this review is to summarize recent advances in our understanding of the role of different adipokines on bone metabolism. METHODS This is a comprehensive review of the literature available in PubMED and Cochrane databases, with an emphasis on the last five years using the keywords. RESULTS Leptin has shown some positive effects on bone metabolism; in contrast, both adiponectin and chemerin have consistently shown a negative association with BMD. No significant association was found between resistin and BMD. Novel adipokines such as visfatin, LCN-2, Nesfatin-1, RBP-4, apelin, and vaspin have shown bone-protective and osteoanabolic properties that could be translated into therapeutic targets. CONCLUSION New evidence suggests the potential role of novel adipokines as biomarkers to predict osteoporosis risk, and as therapeutic targets for the treatment of osteoporosis.
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Affiliation(s)
- Fnu Deepika
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX 77030, USA
| | - Siresha Bathina
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX 77030, USA
| | - Reina Armamento-Villareal
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX 77030, USA
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Obesity and Bone Health: A Complex Relationship. Int J Mol Sci 2022; 23:ijms23158303. [PMID: 35955431 PMCID: PMC9368241 DOI: 10.3390/ijms23158303] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/21/2022] [Accepted: 07/25/2022] [Indexed: 02/07/2023] Open
Abstract
Recent scientific evidence has shown an increased risk of fractures in patients with obesity, especially in those with a higher visceral adipose tissue content. This contradicts the old paradigm that obese patients were more protected than those with normal weight. Specifically, in older subjects in whom there is a redistribution of fat from subcutaneous adipose tissue to visceral adipose tissue and an infiltration of other tissues such as muscle with the consequent sarcopenia, obesity can accentuate the changes characteristic of this age group that predisposes to a greater risk of falls and fractures. Other factors that determine a greater risk in older subjects with obesity are chronic proinflammatory status, altered adipokine secretion, vitamin D deficiency, insulin resistance and reduced mobility. On the other hand, diagnostic tests may be influenced by obesity and its comorbidities as well as by body composition, and risk scales may underestimate the risk of fractures in these patients. Weight loss with physical activity programs and cessation of high-fat diets may reduce the risk. Finally, more research is needed on the efficacy of anti-osteoporotic treatments in obese patients.
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Integrative Analysis of Exosomal miR-452 and miR-4713 Downregulating NPY1R for the Prevention of Childhood Obesity. DISEASE MARKERS 2022; 2022:2843353. [PMID: 35401881 PMCID: PMC8986441 DOI: 10.1155/2022/2843353] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 02/17/2022] [Accepted: 02/28/2022] [Indexed: 12/25/2022]
Abstract
Neuropeptides are associated with childhood obesity and exploring their regulatory mechanisms may reveal new insights for novel treatments. Childhood obesity data were downloaded from the GEO database and were used to screen for differentially expressed neuropeptides in patients with obesity. NPY1R expression was significantly upregulated in children with obesity compared to children without obesity (p < 0.05). The GEO database was used to filter differentially expressed miRNAs in patients with obesity. And hsa-mir-4713 and hsa-mir-452 were found significantly downregulated in adipose tissue. The GEO, TRRUST, and TFacts databases were used to screen all transcription factors for differentially expressed genes (DEGs). The potential regulatory networks between the differentially expressed miRNAs, TFs, and neuropeptides were mapped. In the constructed NPY1R regulatory network, the transcription factors TCF4, HEY1, and GATA3 are significantly associated with NPY1R. TCF4 and HEY1 were positively correlated with NPY1R, while GATA3 was negatively correlated with NPY1R. In the clinical peripheral blood samples, NPY1R, TCF4, and HEY1 were significantly more expressed in the obesity and the obesity with fracture group compared to the control group, while there was no statistically significant difference between the obesity group and the obesity with fracture group in terms of expression. The expression of GATA3, miR-452, and miR-4713 was also significantly lower in the obesity and the obesity with fracture groups when compared to the NC group. Therefore, NPY1R, TCF4, HEY1, GATA3, miR-452, and miR-4713 may be risk factors for fracture in obese children. The potential NPY1R regulatory function was exerted by two pathways: positive regulation caused by TCF4 and HEY1 acting on miR-4713 and negative regulation via GATA3 acting on miR-452. Potential NPY1R-related targets for the treatment of childhood obesity were provided in this study.
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Yamaguchi JT, Weiner JA, Minardi S, Greene AC, Ellenbogen DJ, Hallman MJ, Shah VP, Weisz KM, Jeong S, Nandurkar T, Yun C, Hsu WK, Hsu EL. Characterizing the host response to rhPDGF-BB in a rat spinal arthrodesis model. JOR Spine 2021; 4:e1173. [PMID: 35005440 PMCID: PMC8717117 DOI: 10.1002/jsp2.1173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 09/09/2021] [Accepted: 09/16/2021] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Due to the constraints surrounding autograft bone, surgeons have turned to osteoinductive agents to augment spinal fusion. Reports of complications and questionable efficacy slowed the adoption of these alternatives. Recombinant human platelet-derived growth factor B homodimer (rhPDGF-BB) has been Food and Drug Administration (FDA)-approved (Augment) to promote fusion in other areas of orthopedics, but its characterization in spine fusion has not yet been tested. The purpose of this study is to characterize the host response to PDGF-BB in vivo. METHODS Eighty female Fischer rats underwent L4-5 posterolateral fusion using one of four implant types: (a) iliac crest syngeneic allograft harvested from syngeneic donors, (b) β-TCP/bovine collagen matrix (β-TCP/Col) with sodium acetate buffer, (c) β-TCP/Col with 0.3 mg/mL "low dose," or (d) β-TCP/Col with 3.0 mg/mL "high dose" of rhPDGF-BB. Animals underwent magnetic resonance imaging (MRI) and serum cytokine quantification at 4, 7, 10, and 21 days, postoperatively. Tissues were processed for immunofluorescence staining for Ki67 and von Willebrand factor (vWF) to assess neovascularization. RESULTS MRI demonstrated no differences in fluid accumulation among the four treatment groups at any of the time points. Serum cytokine analysis showed no clinically significant differences between treatment groups in 20 of the 27 cytokines. Inflammatory cytokines IFN-γ, IL-1β, IL-18, MCP-1, MIP-1α, TNF-α were not induced by rhPDGF-BB. Histology showed no differences in cell infiltration, and Ki67 and vWF immunofluorescence staining was similar among groups. CONCLUSIONS rhPDGF-BB delivered with a β-TCP/Col matrix exerts no exaggerated systemic or local host inflammatory response when compared to iliac crest syngeneic allograft bone or the control carrier. rhPDGF-BB mixed with a β-TCP/Col matrix could be a viable and safe biologic alternative to syngeneic allograft in spine fusion. Further studies need to be performed to evaluate efficacy in this setting.
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Affiliation(s)
- Jonathan T. Yamaguchi
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
- Simpson Querrey InstituteFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
| | - Joseph A. Weiner
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
| | - Silvia Minardi
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
- Simpson Querrey InstituteFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
| | - Allison C. Greene
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
- Simpson Querrey InstituteFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
| | - David J. Ellenbogen
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
- Simpson Querrey InstituteFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
| | - Mitchell J. Hallman
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
- Simpson Querrey InstituteFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
| | - Vivek P. Shah
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
- Simpson Querrey InstituteFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
| | - Kevin M. Weisz
- Department of Orthopaedic SurgeryWilliam Beuamont HospitalRoyal OakMichiganUSA
| | - Soyeon Jeong
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
- Simpson Querrey InstituteFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
| | - Tejas Nandurkar
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
- Simpson Querrey InstituteFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
| | - Chawon Yun
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
- Simpson Querrey InstituteFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
| | - Wellington K. Hsu
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
- Simpson Querrey InstituteFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
| | - Erin L. Hsu
- Department of Orthopaedic SurgeryFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
- Simpson Querrey InstituteFeinberg School of Medicine, Northwestern UniversityChicagoIllinoisUSA
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Nikanfar S, Oghbaei H, Rastgar Rezaei Y, Zarezadeh R, Jafari-Gharabaghlou D, Nejabati HR, Bahrami Z, Bleisinger N, Samadi N, Fattahi A, Nouri M, Dittrich R. Role of adipokines in the ovarian function: Oogenesis and steroidogenesis. J Steroid Biochem Mol Biol 2021; 209:105852. [PMID: 33610800 DOI: 10.1016/j.jsbmb.2021.105852] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 12/28/2020] [Accepted: 01/30/2021] [Indexed: 01/02/2023]
Abstract
Adipokines are mainly produced by adipose tissue; however, their expression has been reported in other organs including female reproductive tissues. Therefore, adipokines have opened new avenues of research in female fertility. In this regard, studies reported different roles for certain adipokines in ovarian function, although the role of other recently identified adipokines is still controversial. It seems that adipokines are essential for normal ovarian function and their abnormal levels could be associated with ovarian-related disorders. The objective of this study is to review the available information regarding the role of adipokines in ovarian functions including follicular development, oogenesis and steroidogenesis and also their involvement in ovary-related disorders.
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Affiliation(s)
- Saba Nikanfar
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hajar Oghbaei
- Department of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yeganeh Rastgar Rezaei
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Zarezadeh
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Davoud Jafari-Gharabaghlou
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamid Reza Nejabati
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zahra Bahrami
- Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nathalie Bleisinger
- Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander University of Erlangen, Nürnberg, Erlangen, Germany
| | - Naser Samadi
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Fattahi
- Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander University of Erlangen, Nürnberg, Erlangen, Germany; Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Mohammad Nouri
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Ralf Dittrich
- Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander University of Erlangen, Nürnberg, Erlangen, Germany
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Abstract
Obesity and obesity-related diseases like type 2 diabetes (T2D) are prominent global health issues; therefore, there is a need to better understand the mechanisms underlying these conditions. The onset of obesity is characterized by accumulation of proinflammatory cells, including Ly6chi monocytes (which differentiate into proinflammatory macrophages) and neutrophils, in metabolic tissues. This shift toward chronic, low-grade inflammation is an obese-state hallmark and highly linked to metabolic disorders and other obesity comorbidities. The mechanisms that induce and maintain increased inflammatory myelopoiesis are of great interest, with a recent focus on how obesity affects more primitive hematopoietic cells. The hematopoietic system is constantly replenished by proper regulation of hematopoietic stem and progenitor (HSPC) pools in the BM. While early research suggests that chronic obesity promotes expansion of myeloid-skewed HSPCs, the involvement of the hematopoietic stem cell (HSC) niche in regulating obesity-induced myelopoiesis remains undefined. In this review, we explore the role of the multicellular HSC niche in hematopoiesis and inflammation, and the potential contribution of this niche to the hematopoietic response to obesity. This review further aims to summarize the potential HSC niche involvement as a target of obesity-induced inflammation and a driver of obesity-induced myelopoiesis.
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Lespessailles E, Paccou J, Javier RM, Thomas T, Cortet B. Obesity, Bariatric Surgery, and Fractures. J Clin Endocrinol Metab 2019; 104:4756-4768. [PMID: 30901056 DOI: 10.1210/jc.2018-02084] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 03/13/2019] [Indexed: 12/14/2022]
Abstract
CONTEXT Obesity and its associated comorbidities are a recognized and growing public health problem. For a long time, obesity-associated effects on bone were considered to strengthen the bone, mainly because of the known relationship between body weight and bone mass and the long-term weight-bearing load effect on bone. However, recent epidemiologic studies have shown that obesity may not have a fully protective effect on the occurrence of fragility fractures. The goal of this article is to review updated information on the link between obesity, bariatric surgery, and fractures. METHODS The primary source literature for this review was acquired by searching a published database for reviews and articles up to January 2018. Additional references were selected through the in-depth analysis of the relevant studies. RESULTS We present data showing that overweight and obesity are often encountered in fracture cases. We also analyzed possible reasons and risk factors for fractures associated with overweight and patients with obesity. In addition, this review focuses on the complex effects of dramatic changes in body composition when interpreting dual-energy X-ray absorptiometry readings and findings. Finally, we review the data on the effects and consequences of bariatric surgery on bone metabolism and the risk of fractures in patients undergoing these procedures. CONCLUSION Because of various adiposity-induced effects, patients with obesity are at risk for fracture in certain sites. Bariatric surgery increases the risk of fractures in patients undergoing malabsorptive procedures.
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Affiliation(s)
- Eric Lespessailles
- Department of Rheumatology, Regional Hospital of Orleans, University of Orleans, Orleans, France
| | - Julien Paccou
- Department of Rheumatology, University Hospital of Lille, University of Lille, Lille, France
| | - Rose-Marie Javier
- Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France
| | - Thierry Thomas
- Department of Rheumatology, Nord Hospital, University Hospital of St-Etienne, University of Lyon, Saint-Etienne, France
| | - Bernard Cortet
- Department of Rheumatology, University Hospital of Lille, University of Lille, Lille, France
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11
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Keune JA, Branscum AJ, Wong CP, Iwaniec UT, Turner RT. Effect of Leptin Deficiency on the Skeletal Response to Hindlimb Unloading in Adult Male Mice. Sci Rep 2019; 9:9336. [PMID: 31249331 PMCID: PMC6597714 DOI: 10.1038/s41598-019-45587-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 06/06/2019] [Indexed: 12/29/2022] Open
Abstract
Based on body weight, morbidly obese leptin-deficient ob/ob mice have less bone than expected, suggesting that leptin plays a role in the skeletal response to weight bearing. To evaluate this possibility, we compared the skeletal response of wild type (WT) and ob/ob mice to hindlimb unloading (HU). Mice were individually housed at 32 °C (thermoneutral) from 4 weeks of age (rapidly growing) to 16 weeks of age (approaching skeletal maturity). Mice were then randomized into one of 4 groups (n = 10/group): (1) WT control, (2) WT HU, (3) ob/ob control, and (4) ob/ob HU and the results analyzed by 2-way ANOVA. ob/ob mice pair-fed to WT mice had normal cancellous bone volume fraction (BV/TV) in distal femur, lower femur length and total bone area, mineral content (BMC) and density (BMD), and higher cancellous bone volume fraction in lumbar vertebra (LV). HU resulted in lower BMC and BMD in total femur, and lower BV/TV in distal femur and LV in both genotypes. Cancellous bone loss in femur in both genotypes was associated with increases in osteoclast-lined bone perimeter. In summary, leptin deficiency did not attenuate HU-induced osteopenia in male mice, suggesting that leptin is not required for bone loss induced by unweighting.
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Affiliation(s)
- Jessica A. Keune
- 0000 0001 2112 1969grid.4391.fSkeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331 USA
| | - Adam J. Branscum
- 0000 0001 2112 1969grid.4391.fBiostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331 USA
| | - Carmen P. Wong
- 0000 0001 2112 1969grid.4391.fSkeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331 USA
| | - Urszula T. Iwaniec
- 0000 0001 2112 1969grid.4391.fSkeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331 USA ,0000 0001 2112 1969grid.4391.fCenter for Healthy Aging Research, Oregon State University, Corvallis, OR 97331 USA
| | - Russell T. Turner
- 0000 0001 2112 1969grid.4391.fSkeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331 USA ,0000 0001 2112 1969grid.4391.fCenter for Healthy Aging Research, Oregon State University, Corvallis, OR 97331 USA
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12
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Gender-specific association of body composition with inflammatory and adipose-related markers in healthy elderly Europeans from the NU-AGE study. Eur Radiol 2019; 29:4968-4979. [PMID: 30715588 PMCID: PMC6682581 DOI: 10.1007/s00330-018-5973-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 11/22/2018] [Accepted: 12/14/2018] [Indexed: 01/17/2023]
Abstract
Objectives The aim of this work was to examine the cross-sectional relationship between body composition (BC) markers for adipose and lean tissue and bone mass, and a wide range of specific inflammatory and adipose-related markers in healthy elderly Europeans. Methods A whole-body dual-energy X-ray absorptiometry (DXA) scan was made in 1121 healthy (65–79 years) women and men from five European countries of the “New dietary strategies addressing the specific needs of elderly population for a healthy aging in Europe” project (NCT01754012) cohort to measure markers of adipose and lean tissue and bone mass. Pro-inflammatory (IL-6, IL-6Rα, TNF-α, TNF-R1, TNF-R2, pentraxin 3, CRP, alpha-1-acid glycoprotein, albumin) and anti-inflammatory (IL-10, TGF-β1) molecules as well as adipose-related markers such as leptin, adiponectin, ghrelin, and resistin were measured by magnetic bead-based multiplex-specific immunoassays and biochemical assays. Results BC characteristics were different in elderly women and men, and more favorable BC markers were associated with a better adipose-related inflammatory profile, with the exception of skeletal muscle mass index. No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-β1, TNF-α, IL-6Rα, glycoprotein 130, TNF-α-R1, and TNF-α-R2. Conclusions The association between BC and inflammatory and adipose-related biomarkers is crucial in decoding aging and pathophysiological processes, such as sarcopenia. DXA can help in understanding how the measurement of fat and muscle is important, making the way from research to clinical practice. Key Points • Body composition markers concordantly associated positively or negatively with adipose-related and inflammatory markers, with the exception of skeletal muscle mass index. • No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-β1, TNF-α, IL-6Rα, gp130, TNF-α-R1, and TNF-α-R2. • Skeletal muscle mass index (SMI) shows a good correlation with inflammatory profile in age-related sarcopenia. Electronic supplementary material The online version of this article (10.1007/s00330-018-5973-2) contains supplementary material, which is available to authorized users.
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13
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Ruys CA, van de Lagemaat M, Lafeber HN, Rotteveel J, Finken MJJ. Leptin and IGF-1 in relation to body composition and bone mineralization of preterm-born children from infancy to 8 years. Clin Endocrinol (Oxf) 2018; 89:76-84. [PMID: 29727484 DOI: 10.1111/cen.13733] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 04/03/2018] [Accepted: 04/24/2018] [Indexed: 01/12/2023]
Abstract
OBJECTIVE Preterm birth has been associated with altered body composition, especially increased fat mass (FM) and decreased bone mineralization, and leptin and IGF-1 have been suggested to be involved in the regulation of both. We aimed to study the interplay between leptin, IGF-1, FM and bone mineralization measured in infancy and childhood of children born preterm. DESIGN Observational study. PATIENTS/SUBJECTS Seventy-nine (40 boys) preterm-born children (gestational age ≤32 weeks and/or birth weight ≤1500 g) aged 8 years. MEASUREMENTS Serum leptin and IGF-1 were measured at term age, at 3- and 6-month corrected age (CA), and 8 years. Body composition (fat and lean mass) and bone parameters (bone area, mineral content and density) were measured by Dual-energy X-ray Absorptiometry (DXA) at term age, 6-month CA and 8 years. RESULTS Leptin was positively associated with FM at all time points and with bone parameters at term age and 6-month CA. IGF-1 was associated with body composition and bone density at most of the time points. Explained variation in bone mineralization increased significantly by adding bone area (BA) and height to the models. CONCLUSIONS During infancy and childhood, leptin and IGF-1 were associated with body composition in preterm-born children. In addition, leptin was associated with bone parameters in early infancy, but not in childhood. It is hypothesized that a complicated interplay between multiple pathways, which most likely changes over time, is involved in regulation of body composition and bone mineralization of preterm-born infants.
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Affiliation(s)
- Charlotte A Ruys
- Department of Pediatrics/Neonatology, VU University Medical Center, Amsterdam, The Netherlands
| | - Monique van de Lagemaat
- Department of Pediatrics/Neonatology, VU University Medical Center, Amsterdam, The Netherlands
| | - Harrie N Lafeber
- Department of Pediatrics/Neonatology, VU University Medical Center, Amsterdam, The Netherlands
| | - Joost Rotteveel
- Department of Pediatric Endocrinology, VU University Medical Center, Amsterdam, The Netherlands
| | - Martijn J J Finken
- Department of Pediatric Endocrinology, VU University Medical Center, Amsterdam, The Netherlands
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14
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Firth EC, Gamble GD, Cornish J, Vickers MH. Neonatal leptin treatment reverses the bone-suppressive effects of maternal undernutrition in adult rat offspring. Sci Rep 2017; 7:7686. [PMID: 28794412 PMCID: PMC5550441 DOI: 10.1038/s41598-017-07500-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 06/29/2017] [Indexed: 11/19/2022] Open
Abstract
Alterations in the early life environment, including maternal undernutrition (UN) during pregnancy, can lead to increased risk of metabolic and cardiovascular disorders in offspring. Leptin treatment of neonates born to UN rats reverses the programmed metabolic phenotype, but the possible benefits of this treatment on bone tissue have not been defined. We describe for the first time the effects of neonatal leptin treatment on bone in adult offspring following maternal UN. Offspring from either UN or ad libitum-fed (AD) rats were treated with either saline or leptin (2.5 µg/ g.d on postnatal days (D)3–13) and were fed either a chow or high fat (HF) diet from weaning until study completion at D170. Analysis of micro-tomographic data of the left femur showed highly significant effects of UN on cortical and trabecular bone tissue indices, contributing to inferior microstructure and bone strength, almost all of which were reversed by early leptin life treatment. The HF fat diet negatively affected trabecular bone tissue, but the effects of only trabecular separation and number were reversed by leptin treatment. The negative effects of maternal UN on skeletal health in adult offspring might be prevented or attenuated by various interventions including leptin. Establishment of a minimal efficacious leptin dose warrants further study.
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Affiliation(s)
- Elwyn C Firth
- Liggins Institute, University of Auckland, Auckland, New Zealand. .,Department of Exercise Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand.
| | - Greg D Gamble
- Bone and Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Jillian Cornish
- Bone and Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Mark H Vickers
- Liggins Institute, University of Auckland, Auckland, New Zealand
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15
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Sobacchi C, Palagano E, Villa A, Menale C. Soluble Factors on Stage to Direct Mesenchymal Stem Cells Fate. Front Bioeng Biotechnol 2017; 5:32. [PMID: 28567372 PMCID: PMC5434159 DOI: 10.3389/fbioe.2017.00032] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 04/27/2017] [Indexed: 12/17/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent stromal cells that are identified by in vitro plastic adherence, colony-forming capacity, expression of a panel of surface molecules, and ability to differentiate at least toward osteogenic, adipogenic, and chondrogenic lineages. They also produce trophic factors with immunomodulatory, proangiogenic, and antiapoptotic functions influencing the behavior of neighboring cells. On the other hand, a reciprocal regulation takes place; in fact, MSCs can be isolated from several tissues, and depending on the original microenvironment and the range of stimuli received from there, they can display differences in their essential characteristics. Here, we focus mainly on the bone tissue and how soluble factors, such as growth factors, cytokines, and hormones, present in this microenvironment can orchestrate bone marrow-derived MSCs fate. We also briefly describe the alteration of MSCs behavior in pathological settings such as hematological cancer, bone metastasis, and bone marrow failure syndromes. Overall, the possibility to modulate MSCs plasticity makes them an attractive tool for diverse applications of tissue regeneration in cell therapy. Therefore, the comprehensive understanding of the microenvironment characteristics and components better suited to obtain a specific MSCs response can be extremely useful for clinical use.
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Affiliation(s)
- Cristina Sobacchi
- Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Milan Unit, Milan, Italy.,Human Genome Laboratory, Humanitas Clinical and Research Institute, Rozzano, Milan, Italy
| | - Eleonora Palagano
- Human Genome Laboratory, Humanitas Clinical and Research Institute, Rozzano, Milan, Italy.,Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy
| | - Anna Villa
- Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Milan Unit, Milan, Italy.,Human Genome Laboratory, Humanitas Clinical and Research Institute, Rozzano, Milan, Italy
| | - Ciro Menale
- Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Milan Unit, Milan, Italy.,Human Genome Laboratory, Humanitas Clinical and Research Institute, Rozzano, Milan, Italy
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16
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Hamrick MW. Role of the Cytokine-like Hormone Leptin in Muscle-bone Crosstalk with Aging. J Bone Metab 2017; 24:1-8. [PMID: 28326295 PMCID: PMC5357607 DOI: 10.11005/jbm.2017.24.1.1] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 12/20/2016] [Indexed: 12/14/2022] Open
Abstract
The cytokine-like hormone leptin is a classic adipokine that is secreted by adipocytes, increases with weight gain, and decreases with weight loss. Additional studies have, however, shown that leptin is also produced by skeletal muscle, and leptin receptors are abundant in both skeletal muscle and bone-derived mesenchymal (stromal) stem cells. These findings suggest that leptin may play an important role in muscle-bone crosstalk. Leptin treatment in vitro increases the expression of myogenic genes in primary myoblasts, and leptin treatment in vivo increases the expression of microRNAs involved in myogenesis. Bone marrow adipogenesis is associated with low bone mass in humans and rodents, and leptin can reduce marrow adipogenesis centrally through its receptors in the hypothalamus as well as directly via its receptors in bone marrow stem cells. Yet, central leptin resistance can increase with age, and low circulating levels of leptin have been observed among the frail elderly. Thus, aging appears to significantly alter leptin-mediated crosstalk among various organs and tissues. Aging is associated with bone loss and muscle atrophy, contributing to frailty, postural instability, and the incidence of falls. Therapeutic interventions such as protein and amino acid supplementation that can increase muscle mass and muscle-derived leptin may have multiple benefits for the elderly that can potentially reduce the incidence of falls and fractures.
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Affiliation(s)
- Mark W. Hamrick
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA
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17
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Associations of TNF-α and IL-6 polymorphisms with osteoporosis through joint effects and interactions with LEPR gene in Taiwan: Taichung Community Health Study for Elders (TCHS-E). Mol Biol Rep 2016; 43:1179-91. [PMID: 27401061 DOI: 10.1007/s11033-016-4037-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 07/06/2016] [Indexed: 10/21/2022]
Abstract
Osteoporosis (OST) is a complex multifactorial disease considered to result from interactions of multiple gene and environmental factors. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 are pleiotropic cytokines essential for bone remodeling; and hormone leptin has immunomodulatory effects that stimulate the synthesis of IL-6 and TNF-α. Leptin is involved in the modulation of bone growth and turnover; and its actions are bound by leptin receptor (LEPR). Prior studies evaluated the effects of TNF-α, IL-6, and LEPR gene polymorphisms separately on bone mineral densities (BMD) or OST. In this study, we assessed the roles of TNF-α and IL-6 gene polymorphisms in OST through joint effects and interactions with LEPR gene. We also evaluated possible joint effects and interactions between these polymorphisms and physical activity. Ten tag-SNPs (rs1799964, rs1800629, rs3093662 in TNF-α; rs1880243, rs1800796, rs1554606 in IL-6; and rs1751492, rs8179183, rs1805096, rs1892534 in LEPR) were used to genotype 103 OST cases and 369 controls. BMD of lumbar spine (LS), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry. Our data showed that TNF-α and IL-6 polymorphisms were associated with overall and site-specific OST in both sexes, and that these associations were dependent on rs1805096 and rs1892534 genotypes of LEPR. In men, LEPR A-G-G-G haplotype was associated with FN OST (OR 4.65, 95 % CI 1.61-13.40, p = 0.004). Genotype AA/AG of LEPR rs1751492 was associated with overall and FN OST in women without physical activity, but not in women with physical activity (p < 0.05 for interaction between physical activity and LEPR rs1751492). In men, we detected significant interactions of IL-6 rs1800796 with LEPR rs1805096 and rs1892534 for FN and TH OST (all p < 0.05). Our data indicate that LEPR gene may play joint and interactive roles with TNF-α and IL-6 genes and physical inactivity in development of OST. Haplotype analyses revealed that the correlations tended to be prominent in men with FN OST.
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18
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Wang L, Sun S, Yang L, Lu C, Cao XJ. Effects of leptin on femoral fracture in rats. J Biomed Res 2016; 32:130-135. [PMID: 28550273 PMCID: PMC5895567 DOI: 10.7555/jbr.31.20160077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
In this study, our objective was to evaluate effects of leptin on fracture healing in rats. Seventy two male Sprague-Dawley (SD) rats were randomized into 3 groups. Standardized femoral fractures were created in all the rats. Group A was treated with 1 mL normal saline (NS), group B with 0.3 μg/kg leptin in 1 mL NS, and group C with 0.5 μg/kg leptin in 1 mL NS for 2 weeks intraperitoneally. Each group was divided into three subgroups including 8 rats for evaluation at 2, 4 and 8 weeks. Radiological evaluation showed that callus formation of group B and C was all significantly higher than group A at 8 weeks (P=0.04 and P=0.013, respectively). There was no statistically significant difference in fracture healing between group B and group C at 8 weeks (P=0.197). Histological evaluation revealed fracture healing of group B and C was better than group A at 4 weeks (P=0.01 and P=0.002, respectively) and 8 weeks (P=0.008 and P=0.003, respectively). Micro-computed tomography (Micro-CT) analysis demonstrated that greater amounts of bony callus and evidence of bone fusion were observed in group B and C at 4 weeks (P=0.02 and P=0.04, respectively) and 8 weeks (P=0.005 and P=0.001, respectively) compared to group A. Group C also had better fracture healing than group B at 8 weeks (P=0.01). In conclusion, leptin has a positive effect on rat femoral fracture healing.
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Affiliation(s)
- Lei Wang
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Sixin Sun
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Lei Yang
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Chun Lu
- Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Xiao-Jian Cao
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
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19
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Mpalaris V, Anagnostis P, Anastasilakis AD, Goulis DG, Doumas A, Iakovou I. Serum leptin, adiponectin and ghrelin concentrations in post-menopausal women: Is there an association with bone mineral density? Maturitas 2016; 88:32-6. [PMID: 27105694 DOI: 10.1016/j.maturitas.2016.03.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2015] [Revised: 01/29/2016] [Accepted: 03/03/2016] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Adipokines and ghrelin exert well-documented effects on energy expenditure and glucose metabolism. Experimental data also support a role in bone metabolism, although data from clinical studies are conflicting. The purpose of this cross-sectional study was to investigate the association of serum concentrations of leptin, adiponectin and ghrelin with bone mineral density (BMD) in post-menopausal women. METHODS BMD in lumbar spine and femoral neck, and circulating leptin, adiponectin and ghrelin concentrations were measured in 110 healthy post-menopausal women. Patients with secondary causes of osteoporosis were excluded. RESULTS Osteoporosis was diagnosed in 30 (27%) women and osteopenia in 54 (49%). Serum leptin concentrations were positively correlated with both lumbar spine (r=0.343, p<0.01) and femoral neck BMD (r=0.370, p<0.01). Adiponectin concentrations were negatively associated with BMD at both sites (r=-0.321, p<0.01 and r=-0.448, p<0.01 respectively). No significant correlation between ghrelin concentrations and BMD was found. Osteoporotic women had lower body weight, body mass index (BMI) and leptin concentrations, but higher adiponectin concentrations compared with non-osteoporotic women. In multivariate stepwise regression analysis, the association of adiponectin concentrations with BMD remained significant only for femoral neck, after adjustment for body weight or BMI. CONCLUSIONS An inverse association between adiponectin and femoral neck BMD was found in post-menopausal women, independently of body weight. The positive association between leptin and BMD was dependent on body weight, whereas no effect of ghrelin on BMD was evident.
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Affiliation(s)
- V Mpalaris
- Department of Nuclear Medicine, Aristotle University, Papageorgiou Hospital, 56403 Thessaloniki, Greece
| | - P Anagnostis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece
| | - A D Anastasilakis
- Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece
| | - D G Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece
| | - A Doumas
- Department of Nuclear Medicine, Aristotle University, Papageorgiou Hospital, 56403 Thessaloniki, Greece
| | - I Iakovou
- Department of Nuclear Medicine, Aristotle University, Papageorgiou Hospital, 56403 Thessaloniki, Greece.
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20
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Lange-Consiglio A, Corradetti B, Perrini C, Bizzaro D, Cremonesi F. Leptin and leptin receptor are detectable in equine spermatozoa but are not involved in in vitro fertilisation. Reprod Fertil Dev 2016; 28:574-85. [DOI: 10.1071/rd14130] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2014] [Accepted: 08/15/2014] [Indexed: 12/21/2022] Open
Abstract
In human and swine, leptin (OB) has been identified in seminal plasma and leptin receptors (OB-R) on the cell surface of spermatozoa, indicating that spermatozoa are a target for OB. This hormone has also been detected in follicular fluid (FF) in women and mares, although its role requires further study. The aims of this study were to investigate the immunolocalisation and the expression of OB and OB-R in equine spermatozoa and to evaluate the involvement of OB in equine in vitro fertilisation (IVF). Since progesterone (P) and OB are both found in FF, the individual and combined effects of these two hormones were studied in equine IVF and compared with the results obtained from the use of FF for in vitro sperm preparation. For the first time, we were able to identify OB and OB-R mRNA and their corresponding proteins in equine spermatozoa. When spermatozoa were treated with OB, there was a decrease in the three motility parameters VSL, STR and LIN, commonly associated with hyperactivation, whilst the acrosome reaction rate increased (P < 0.05). The fertilisation rate was 51% with FF, 46.15% with P, 43.64% with P+OB and 0% with OB alone. The percentage of eight-cell stage embryos was 18.7% with FF, 17.1% with P and 16.7% with OB+P. OB alone did not permit oocyte fertilisation, indicating that, in the horse, OB is involved in capacitation and hyperactivation but not in sperm penetration.
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21
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Greco EA, Lenzi A, Migliaccio S. The pathophysiological basis of bone tissue alterations associated with eating disorders. Horm Mol Biol Clin Investig 2016; 28:121-132. [DOI: 10.1515/hmbci-2016-0006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Accepted: 02/09/2016] [Indexed: 12/13/2022]
Abstract
AbstractAnorexia nervosa (AN) and obesity are two major eating disorders present nowadays in Western countries. They are both characterized by striking body composition variations and hormonal alterations, which impact on skeletal metabolism, inducing bone tissue modifications and, thus, often cause an increased risk for fractures. AN and obesity are characterized by a severe reduction in fat mass and a high expression of it, respectively, and in both conditions hormones secreted or modulated by body fat content are important determinants of low bone density, impaired bone structure and reduced bone strength. In addition, in both AN and obesity, increased marrow adiposity, which correlates with low bone density, has been observed. This review will discuss the pathophysiological basis of bone alterations associated with AN and obesity, conditions of extreme energy deficiency and excess, respectively.
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Abstract
During the last decades, obesity and osteoporosis have become important global health problems, and the belief that obesity is protective against osteoporosis has recently come into question. In fact, some recent epidemiologic and clinical studies have shown that a high level of fat mass might be a risk factor for osteoporosis and fragility fractures. Several potential mechanisms have been proposed to explain the complex relationship between adipose tissue and bone. Indeed, adipose tissue secretes various molecules, named adipokines, which are thought to have effects on metabolic, skeletal and cardiovascular systems. Moreover, fat tissue is one of the major sources of aromatase, an enzyme that synthesizes estrogens from androgen precursors, hormones that play a pivotal role in the maintenance of skeletal homeostasis, protecting against osteoporosis. Moreover, bone cells express several specific hormone receptors and recent observations have shown that bone-derived factors, such as osteocalcin and osteopontin, affect body weight control and glucose homeostasis. Thus, the skeleton is considered an endocrine target organ and an endocrine organ itself, likely influencing other organs as well. Finally, adipocytes and osteoblasts originate from a common progenitor, a pluripotential mesenchymal stem cell, which has an equal propensity for differentiation into adipocytes or osteoblasts (or other lines) under the influence of several cell-derived transcription factors. This review will highlight recent insights into the relationship between fat and bone, evaluating both potential positive and negative influences between adipose and bone tissue. It will also focus on the hypothesis that osteoporosis might be considered the obesity of bone.
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Affiliation(s)
- Emanuela A. Greco
- Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, ‘Sapienza’ University of Rome, Rome, Italy
| | - Andrea Lenzi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, ‘Sapienza’ University of Rome, Rome, Italy
| | - Silvia Migliaccio
- Unit of Endocrinology, Department of Movement, Human and Health Sciences, Section of Health Sciences, ‘Foro Italico’ University of Rome, Largo Lauro De Bosis 15, 00195 Rome, Italy
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Wang L, Liu L, Pan Z, Zeng Y. Serum leptin, bone mineral density and the healing of long bone fractures in men with spinal cord injury. Bosn J Basic Med Sci 2015; 15:69-74. [PMID: 26614856 DOI: 10.17305/bjbms.2015.693] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Revised: 10/16/2015] [Accepted: 10/17/2015] [Indexed: 11/16/2022] Open
Abstract
Previously reported fracture rates in patients with spinal cord injury range from 1% to 20%. However, the exact role of spinal cord injury in bone metabolism has not yet been clarified. In order to investigate the effects of serum leptin and bone mineral density on the healing of long bone fractures in men with spinal cord injury, 15 male SCI patients and 15 matched controls were involved in our study. The outcome indicated that at 4 and 8 weeks after bone fracture, callus production in patients with spinal cord injury was lower than that in controls. Besides, bone mineral density was significantly reduced at 2, 4 and 8 weeks. In addition, it was found that at each time point, patients with spinal cord injury had significantly higher serum leptin levels than controls and no association was found between serum leptin level and bone mineral density of lumbar vertebrae. Moreover, bone mineral density was positively correlated with bone formation in both of the groups. These findings suggest that in early phases i.e. week 4 and 8, fracture healing was impaired in patients with spinal cord injury and that various factors participated in the complicated healing process, such as hormonal and mechanical factors.
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Affiliation(s)
- Lei Wang
- Department of Orthopedics, the Affiliated People's Hospital of Jiangsu University, China.
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Sabour H, Norouzi Javidan A, Latifi S, Shidfar F, Heshmat R, Emami Razavi SH, Vafa MR, Larijani B. Omega-3 fatty acids' effect on leptin and adiponectin concentrations in patients with spinal cord injury: A double-blinded randomized clinical trial. J Spinal Cord Med 2015; 38:599-606. [PMID: 25096818 PMCID: PMC4535802 DOI: 10.1179/2045772314y.0000000251] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
CONTEXT Omega-3 fatty acids have been recently proposed to induce neural improvement in patients with spinal cord injury (SCI) while affecting some hormones including leptin and adiponectin. OBJECTIVES We tried to evaluate the effect of omega-3 fatty acids on circulatory concentrations of leptin and adiponectin among these patients. DESIGN This study is a double-blinded randomized clinical trial with intervention duration of 14 months. SETTING A tertiary rehabilitation center. PARTICIPANTS Total of 104 patients with SCI who did not meet our exclusion criteria entered the study. Those with history of diabetes, cancer, endocrinology disease, acute infection, and use of special medications were excluded. Patients were divided randomly into the treatment and control group by using permuted balanced block randomization. INTERVENTION The treatment group received two MorDHA® capsules per day (each capsule contain 465 mg of docosahexaenoic acid (DHA) and 63 mg of eicosapentaenoic acid (EPA)) for 14 months while the control group received placebo capsules with similar color, shape, and taste. MAIN OUTCOMES MEASURES Leptin and adiponectin concentrations in plasma were measured at the beginning of trial and then after 6 and 14 months. RESULTS Fourteen months of treatment with DHA and EPA did not influence concentrations of leptin but adiponectin level was significantly decreased (P: 0.03). Weight was positively correlated with leptin level at stage 0 of trial (P: 0.008, r=0.41) while this association was attenuated through stages of trial after intervention. CONCLUSION Our data show that omega-3 fatty acids may not affect plasma concentrations of leptin but adiponectin level is decreased in patients with SCI. Moreover, this intervention influences the linear relationship between weight and leptin after 14 months administration of DHA and EPA.
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Affiliation(s)
- Hadis Sabour
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Norouzi Javidan
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Tehran, Iran
| | - Sahar Latifi
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Tehran, Iran
| | - Farzad Shidfar
- Nutrition Department, Iran University of Medical Sciences, Tehran, Iran
| | - Ramin Heshmat
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed-Hassan Emami Razavi
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Tehran, Iran
| | | | - Bagher Larijani
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Tehran, Iran,Correspondence to: Bagher Larijani, Endocrinology and Metabolism Research Institute, 5th floor, Shariati Hospital, North Kargar Avenue, 1411413137, Tehran, Iran. ;
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Migliaccio S, Greco EA, Wannenes F, Donini LM, Lenzi A. Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal regulation for osteoporosis and obesity development. Horm Mol Biol Clin Investig 2015; 17:39-51. [PMID: 25372729 DOI: 10.1515/hmbci-2013-0070] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Accepted: 02/14/2014] [Indexed: 02/07/2023]
Abstract
The belief that obesity is protective against osteoporosis has recently been revised. In fact, the latest epidemiologic and clinical studies show that a high level of fat mass, but also reduced muscle mass, might be a risk factor for osteoporosis and fragility fractures. Furthermore, increasing evidence seems to indicate that different components such as myokines, adipokines and growth factors, released by both fat and muscle tissues, could play a key role in the regulation of skeletal health and in low bone mineral density and, thus, in osteoporosis development. This review considers old and recent data in the literature to further evaluate the relationship between fat, bone and muscle tissue.
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Tian L, Yu X. Lipid metabolism disorders and bone dysfunction--interrelated and mutually regulated (review). Mol Med Rep 2015; 12:783-94. [PMID: 25760577 PMCID: PMC4438959 DOI: 10.3892/mmr.2015.3472] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 12/03/2014] [Indexed: 02/05/2023] Open
Abstract
The association between lipid and bone metabolism has become an increasing focus of interest in recent years, and accumulating evidence has shown that atherosclerosis (AS) and osteoporosis (OP), a disorder of bone metabolism, frequently co-exist. Fat and bone are known to share a common progenitor cell: Multipotent mesenchymal stem cells (MSC) in the bone marrow (BM), which are able to differentiate into various cell phenotypes, including osteoblasts, adipocytes and chondrocytes. Laboratory-based and clinical trials have shown that increasing adipocytes are accompanied by a decrease in bone mineral density (BMD) and bone mass. Statins, lipid-lowering drugs used to treat hyperlipidemia, also provide benefit in the treatment of OP. There is thus evidence that the metabolism of lipids is correlated with that of bone, and that the two are mutually regulated. The present review primarily focuses on the potential association between lipid metabolism disturbance and OP, based on biological metabolism, pathophysiological processes, results from clinical and experimental animal studies, processes involved in the differentiation of adipocytes and osteoblasts, as well as pharmacological treatments of these diseases.
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Affiliation(s)
- Li Tian
- Laboratory of Endocrinology and Metabolism, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Xijie Yu
- Laboratory of Endocrinology and Metabolism, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
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Mpalaris V, Anagnostis P, Goulis DG, Iakovou I. Complex association between body weight and fracture risk in postmenopausal women. Obes Rev 2015; 16:225-33. [PMID: 25586664 DOI: 10.1111/obr.12244] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Revised: 10/09/2014] [Accepted: 11/03/2014] [Indexed: 11/27/2022]
Abstract
Osteoporosis is a common disease, characterized by low bone mass with micro-architectural disruption and skeletal fragility, resulting in an increased risk of fracture. A substantial number of studies has examined the possible relationship between body weight, bone mineral density and fracture risk in post-menopausal women, with the majority of them concluding that low body weight correlates with increased risk of fracture, especially hip fracture. Controversies about the potential protective effect of obesity on osteoporosis and consequent fracture risk still exist. Several recent studies question the concept that obesity exerts a protective effect against fractures, suggesting that it stands as a risk factor for fractures at specific skeletal sites, such as upper arm. The association between body weight and fracture risk is complex, differs across skeletal sites and body mass index, and is modified by the interaction between body weight and bone mineral density. Some potential explanations that link obesity with increased fracture risk may be the pattern of falls and impaired mobility in obese individuals, comorbidities, such as asthma, diabetes and early menopause, as well as, increased parathyroid hormone and reduced 25-hydroxy-vitamin D concentrations.
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Affiliation(s)
- V Mpalaris
- Third Department of Nuclear Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Elabd S, Sabry I. Two Birds with One Stone: Possible Dual-Role of Oxytocin in the Treatment of Diabetes and Osteoporosis. Front Endocrinol (Lausanne) 2015; 6:121. [PMID: 26322016 PMCID: PMC4530313 DOI: 10.3389/fendo.2015.00121] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Accepted: 07/23/2015] [Indexed: 12/15/2022] Open
Abstract
Oxytocin (OT), a hormone most commonly associated with labor and lactation, may have a wide variety of physiological and pathological functions, which makes OT and its receptor potential targets for drug therapy. In this review, we highlight the newly discovered metabolic role of OT in diabetes and its complication, such as diabetic osteopathy. OT may have positive metabolic effects; this is based on the change in glucose metabolism, lipid profile, and insulin sensitivity. It may modify glucose uptake and insulin sensitivity both through direct and indirect effects. It may also cause regenerative changes in diabetic pancreatic islet cells. Moreover, it has an anabolic effect on the bone biology. So, the activation of the OT receptor pathway by infusion of OT, OT analogs, or OT agonists may represent a promising approach for the treatment of diabetes and some of its complications, including diabetic osteopathy.
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Affiliation(s)
- Seham Elabd
- Human Physiology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
- *Correspondence: Seham Elabd, Department of Human Physiology, Medical Research Institute, Alexandria University, 165, Horreya Avenue, Hadara, Alexandria, Egypt,
| | - Ismail Sabry
- Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt
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Sabour H, Norouzi Javidan A, Latifi S, Shidfar F, Vafa MR, Emami Razavi SH, Larijani B, Heshmat R. Relationship between leptin and adiponectin concentrations in plasma and femoral and spinal bone mineral density in spinal cord-injured individuals. Spine J 2015; 15:1-9. [PMID: 24948038 DOI: 10.1016/j.spinee.2014.06.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Revised: 05/11/2014] [Accepted: 06/09/2014] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Previously, the associations between leptin and adiponectin levels with bone mineral density (BMD) have been reported in different populations, and occasionally, controversial results have been demonstrated. Until now, these relationships in spinal cord-injured individuals have not yet been described. PURPOSE We tried to investigate the correlation between leptin and adiponectin concentrations in plasma and BMD in Iranian patients with spinal cord injury (SCI). STUDY DESIGN/SETTING Cross-sectional investigation. PATIENT SAMPLE Referred patients with SCI who did not meet our exclusion criteria such as pregnancy, lactation, amputation, history of diabetes, cancer, endocrinology disease, and use of special medications entered the study. OUTCOME MEASURES Bone mineral density of femoral neck, trochanter, intertrochanteric zone, total hip, and lumbar vertebrae assessed by dual-energy X-ray absorptiometry and serum leptin and adiponectin levels measured by blood sample analysis using immunoassay techniques. METHODS Patient demographic characteristics were measured during face-to-face visits. Injury level and Spinal cord Injury Association (ASIA) score were assessed by clinical examination and were confirmed by imaging aids. Measured levels of leptin and adiponectin and dual-energy X-ray absorptiometry results were analyzed with partial correlation analysis method after adjustment for weight, body mass index (BMI), and age. RESULTS Total of 104 patients (19 females and 85 males) entered this investigation. Higher leptin concentration was significantly associated with higher BMD in femoral neck (p=.006, r=0.73), femoral intertrochanteric zone (p=.001, r=0.83), and hip (p=.001, r=0.81) only in female patients, whereas no such association was detected in male participants after adjusting for BMI and age. Leptin and adiponectin levels were not associated with lumbar spine BMD in both genders. Neither injury level nor ASIA score and plegia type (paraplegia or tetraplegia) influenced on leptin and adiponectin concentrations. CONCLUSIONS We found no association between leptin concentration and BMD in male individuals, whereas a positive correlation between leptin and BMD of femoral neck, intertrochanter, and hip was observed in female patients that shows a sexual polymorphism in this relationship. However, by considering the low number of female participants, these results should be interpreted cautiously. Lumbar spine BMD was associated with neither leptin nor adiponectin level in both genders.
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Affiliation(s)
- Hadis Sabour
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Abbas Norouzi Javidan
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Sahar Latifi
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Farzad Shidfar
- Department of Nutrition, Iran University of Medical Sciences, Hemat Highway, Tehran, Iran
| | - Mohammad Reza Vafa
- Department of Nutrition, Iran University of Medical Sciences, Hemat Highway, Tehran, Iran
| | - Seyed-Hassan Emami Razavi
- Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, Keshavarz Blvd, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Institute (EMRI), Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran, Iran
| | - Ramin Heshmat
- Endocrinology and Metabolism Research Institute (EMRI), Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran, Iran; Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, No. 111, 19th St, North Karegar, Tehran 14579-65597, Iran.
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Muruganandan S, Sinal CJ. The impact of bone marrow adipocytes on osteoblast and osteoclast differentiation. IUBMB Life 2014; 66:147-155. [PMID: 24638917 DOI: 10.1002/iub.1254] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Accepted: 02/28/2014] [Indexed: 01/07/2023]
Abstract
Throughout life, bone is constantly remodeled through the complementary processes of bone resorption and bone formation. Highly coordinated regulation of these activities is essential for maintaining consistent bone quality and quantity. Normally, the development and function of bone-forming (osteoblast) and bone-resorbing (osteoclast) cells are tightly regulated by signaling molecules secreted by these two cell types. Within the bone marrow microenvironment, osteoblasts arise from mesenchymal stem cells (MSCs), which are in close contact with the hematopoietic stem cell (HSC) precursors that differentiate into mature osteoclasts. Signaling molecules secreted by osteoblasts (e.g., receptor activator of nuclear factor kappa B ligand and osteoprotegerin) and osteoclasts (e.g., bone morphogenetic protein 6, wingless-type MMTV integration site family member 10B, sphingosine-1-phosphate, and ephrin-B2) play a key role in bone remodeling by guiding the differentiation, localization, and function of bone cells. In addition to osteoblasts, bone marrow MSCs can also differentiate into adipocytes that affect bone remodeling by competitively suppressing intracellular osteogenic signals, including runt-related transcription factor 2, osterix, and beta-catenin, while simultaneously promoting the secretion of adipogenic signaling molecules such as leptin, adiponectin, chemerin, omentin-1, resistin, and visfatin. Secreted adipogenic factors have also been shown to affect the osteoclastogenic differentiation of HSCs. Herein, we discuss the impact of bone marrow adipocytes on the coupling of osteoblast and osteoclast differentiation, and the relevance to bone-loss disorders such as osteoporosis. © 2014 IUBMB Life, 66(3):147-155, 2014.
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Affiliation(s)
| | - Christopher J Sinal
- Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
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Hage MP, El-Hajj Fuleihan G. Bone and mineral metabolism in patients undergoing Roux-en-Y gastric bypass. Osteoporos Int 2014; 25:423-39. [PMID: 24008401 DOI: 10.1007/s00198-013-2480-9] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2013] [Accepted: 07/29/2013] [Indexed: 01/06/2023]
Abstract
UNLABELLED Despite effective weight reduction, the impact of bariatric surgery on bone is a major concern. Mechanisms include decreased mechanical loading, calcium and vitamin D malabsorption, deficiency in other nutrients, and alterations in fat- and gut-derived hormones. The evidence to support clinical care pathways to prevent bone loss and fractures is at this point weak. INTRODUCTION There is a growing concern regarding the potential deleterious impact of bariatric surgery on bone metabolism. This comprehensive review addresses this controversial topic. METHODS We reviewed and analyzed articles evaluating bone metabolism and mechanisms for the ensuing putative bone loss in adult patients exclusively undergoing Roux-en-Y gastric bypass (RYGB) surgery, for the period spanning 1942 till September 2012. RESULTS Mechanisms identified to contribute to alterations in bone metabolism after bypass surgery include: decreased mechanical loading, calcium and vitamin D malabsorption with secondary hyperparathyroidism, deficiency in other nutrients, in addition to alterations in adipokines, gonadal steroids, and gut-derived hormones favoring bone loss, with the exception of serotonin and glucagon-like peptide-1. The relative contribution of each of these hormones to changes in bone homeostasis after bypass surgery remains undefined. Bone loss reflected by a decline in bone mineral density (BMD) and an increase in bone turnover markers have been reported in many studies, limited for the most part by the exclusive use of dual energy X-ray absorptiometry. Well-designed long-term prospective trials with fractures as an outcome, and studies investigating the magnitude, reversibility, and impact of the observed metabolic changes on fracture outcomes are lacking. CONCLUSION Robust conclusions regarding bone loss and fracture outcome after RYGB surgery cannot be drawn at this time. Although not evidence based, baseline evaluation and sequential monitoring with measurement of BMD and calciotropic hormones seem appropriate, with adequate calcium and vitamin D replacement. Beneficial interventions remain unclear.
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Affiliation(s)
- M P Hage
- Department of Internal Medicine, Division of Endocrinology, Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, American University of Beirut-Medical Center, PO BOX: 11-0236, Riad El Solh, 1107 2020, Beirut, Lebanon
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Solomon G, Atkins A, Shahar R, Gertler A, Monsonego-Ornan E. Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in the mouse. Am J Physiol Endocrinol Metab 2014; 306:E14-27. [PMID: 24169045 DOI: 10.1152/ajpendo.00155.2013] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Leptin's in vivo effect on the rodent skeleton depends on the model used and the mode of administration. Superactive mouse leptin antagonist (SMLA) was produced and then pegylated (PEG) to prolong and enhance its in vivo activity. We blocked leptin signaling by injecting this antagonist peripherally into normal mice at various time points and studied their metabolic and skeletal phenotypes. Subcutaneous PEG-SMLA injections into 4-wk-old female C57BL/6J mice increased weight gain and food consumption significantly after only 1 mo, and the effect lasted for the 3 mo of the experiment, proving its central inhibiting activity. Mice showed a significant increase in serum glucose, cholesterol, triglycerides, insulin, and HOMA-IR throughout the experiment. Quantification of gene expression in "metabolic" tissues also indicated the development of insulin resistance. Bone analyses revealed a significant increase in trabecular and cortical parameters measured in both the lumbar vertebrae and tibiae in PEG-SMLA-treated mice in the 1st and 3rd months as well as a significant increase in tibia biomechanical parameters. Interestingly, 30 days of treatment with the antagonist in older mice (aged 3 and 6 mo) affected body weight and eating behavior, just as they had in the 1-mo-old mice, but had no effect on bone parameters, suggesting that leptin's effect on bones, either directly or through its obesogenic effect, is dependent upon stage of skeletal development. This potent and reversible antagonist enabled us to study leptin's in vivo role in whole body and bone metabolism and holds potential for future therapeutic use in diseases involving leptin signaling.
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Migliaccio S, Greco EA, Aversa A, Lenzi A. Age-associated (cardio)metabolic diseases and cross-talk between adipose tissue and skeleton: endocrine aspects. Horm Mol Biol Clin Investig 2014; 20:25-38. [DOI: 10.1515/hmbci-2014-0030] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2014] [Accepted: 11/05/2014] [Indexed: 12/20/2022]
Abstract
AbstractAged individuals continue to increase in number, and it is important to understand the pathophysiological mechanisms of age-related changes in order to develop interventions that could contribute to “successful aging”. Metabolic and hormonal factors, age-related changes in body composition, and a decline in physical activity are all involved in the tendency to lose muscle mass, to gain fat mass, and, also, to experience bone loss. Obesity, sarcopenia, and osteoporosis are important widespread health problems that lead to high prevalence of both mortality and morbidity. Indeed, during the last decades, obesity and osteoporosis have become a major health threat around the world. Aging increases the risk of developing obesity, sarcopenia, osteoporosis, and, also, cardiovascular diseases. A reduction of both bone and muscle mass with a corresponding increase of fat mass and inflammation and hormonal imbalance in the elderly lead to and may synergistically increase cardiovascular diseases. This review will focus on the relationship among these different medical situations, trying to clarify the cellular and molecular mechanisms.
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Azevedo-Neto RD, Gonzaga CC, Deliberador TM, Klug LG, Da Costa Oliveira L, Zielak JC, De Andrade Urban C, De Araujo MR, Giovanini AF. Fragmented Adipose Tissue Transplanted to Craniofacial Deformities Induces Bone Repair Associated with Immunoexpression of Adiponectin and Parathyroid Hormone 1-Receptor. Cleft Palate Craniofac J 2013; 50:639-47. [DOI: 10.1597/12-121] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective This study analyzed the influence of autogenous white adipose tissue on bone matrix development in critical-size defects created in rabbit calvaria. Materials and Methods A 15-mm-diameter defect was created in the calvaria of 42 rabbits. Twenty-one rabbits were treated with 86 mm3 of immediate transplant of fragmented white subcutaneous adipose tissue (WSAT); the others constituted the control group (sham). The animals were euthanized at 7, 15, and 40 days postsurgery (n = 7), and the histological data were analyzed by histomorphometry and immunohistochemistry using the anti-adiponectin and parathyroid hormone 1-receptor (PTH1R) antibodies. Results The calvariae treated with fragmented WSAT demonstrated significant bone formation. These results coincided with the significant presence of immunopositivity to adiponectin and PTH1R in loci, which in turn coincided with the increase in bonelike matrix deposited both in fat tissue stroma and adipocytes' cytoplasm. In contrast, the control group revealed a small amount of bone-matrix deposition and presented scarce PTH1R expression and a lack of immunostain for adiponectin. Conclusion These results indicate that transplant of fragmented white subcutaneous adipose tissue may be an alternative to treatment of craniofacial bone deformities because adipose tissue suffers from osseous metaplasia and exhibits immunoexpression of the adiponectin and PTH1R, which are proteins associated with bone metabolism
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Anagnostis P, Vakalopoulou S, Charizopoulou M, Kazantzidou E, Chrysopoulou T, Moka E, Agapidou A, Zournatzi V, Garipidou V. Is there any association between leptin levels and bone mineral density in haemophiliac men? Arch Med Sci 2013; 9:459-65. [PMID: 23847667 PMCID: PMC3701978 DOI: 10.5114/aoms.2013.35341] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2012] [Revised: 07/21/2012] [Accepted: 08/01/2012] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION Conflicting data exist regarding the role of leptin in bone metabolism. The purpose of the present study was to investigate serum leptin concentrations in male patients with haemophilia A and B, a disease known to be associated with low bone mass. MATERIAL AND METHODS Eighty-one male patients, aged 45.4 ±15 years, were screened. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) in lumbar spine (LS), femoral neck (FN) and total hip (TH). RESULTS Low bone mass was diagnosed in 20 patients (24.7%). Serum leptin concentrations were strongly associated with body weight (r s = 0.457, p = 0.0001) and body mass index (BMI) (r s = 0.491, p = 0.0001). In unadjusted analysis leptin was inversely associated with BMD in LS (r s = -0.255, p = 0.023), but not in FN and TH (r s = -0.205, p = 0.068 and r s = -0.191, p = 0.090, respectively). However, after adjusting for BMI and body weight, leptin was inversely associated with BMD in FN (F 1,76 = 7.727, p = 0.007, β = -0.371, ΔR (2) = 0.089) and TH (F 1,76 = 4.533, p = 0.036, β = -0.290, ΔR (2) = 0.054), but not in LS (F 1,75 = 2.076, p = 0.154, β = -0.202, ΔR (2) = 0.026). No association was found between age, presence of HBV, HCV or HIV infection or alkaline phosphatase and leptin levels. CONCLUSIONS Our study showed a negative association between circulating leptin levels and bone mass in males, independently of body weight and BMI.
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Affiliation(s)
| | - Sofia Vakalopoulou
- Division of Haematology, 2 Propaedeutic Department of Internal Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece
| | - Maria Charizopoulou
- Department of Psychology, School of Philosophy, Aristotle University of Thessaloniki, Greece
| | | | | | - Eleni Moka
- Division of Haematology, 2 Propaedeutic Department of Internal Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece
| | - Alexandra Agapidou
- Division of Haematology, 2 Propaedeutic Department of Internal Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece
| | - Vassiliki Zournatzi
- 2 Department of Obstetrics and Gynaecology, Aristotle University, Hippokration General Hospital, Thessaloniki, Greece
| | - Vasilia Garipidou
- Division of Haematology, 2 Propaedeutic Department of Internal Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece
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Biochanin a promotes osteogenic but inhibits adipogenic differentiation: evidence with primary adipose-derived stem cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:846039. [PMID: 23843885 PMCID: PMC3697292 DOI: 10.1155/2013/846039] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/29/2013] [Accepted: 05/28/2013] [Indexed: 01/14/2023]
Abstract
Biochanin A has promising effects on bone formation in vivo, although the underlying mechanism remains unclear yet. This study therefore aimed to investigate whether biochanin A regulates osteogenic and adipogenic differentiation using primary adipose-derived stem cells. The effects of biochanin A (at a physiologically relevant concentration of 0.1-1 μM) were assessed in vitro using various approaches, including Oil red O staining, Nile red staining, alizarin red S staining, alkaline phosphatase (ALP) activity, flow cytometry, RT-PCR, and western blotting. The results showed that biochanin A significantly suppressed adipocyte differentiation, as demonstrated by the inhibition of cytoplasmic lipid droplet accumulation, along with the inhibition of peroxisome proliferator-activated receptor gamma (PPAR γ ), lipoprotein lipase (LPL), and leptin and osteopontin (OPN) mRNA expression, in a dose-dependent manner. On the other hand, treatment of cells with 0.3 μM biochanin A increased the mineralization and ALP activity, and stimulated the expression of the osteogenic marker genes ALP and osteocalcin (OCN). Furthermore, biochanin A induced the expression of runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), and Ras homolog gene family, member A (RhoA) proteins. These observations suggest that biochanin A prevents adipogenesis, enhances osteoblast differentiation in mesenchymal stem cells, and has beneficial regulatory effects in bone formation.
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Scott JPR, Sale C, Greeves JP, Casey A, Dutton J, Fraser WD. Effect of fasting versus feeding on the bone metabolic response to running. Bone 2012; 51:990-9. [PMID: 22960044 DOI: 10.1016/j.bone.2012.08.128] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2012] [Revised: 07/30/2012] [Accepted: 08/22/2012] [Indexed: 11/16/2022]
Abstract
Individuals often perform exercise in the fasted state, but the effects on bone metabolism are not currently known. We compared the effect of an overnight fast with feeding a mixed meal on the bone metabolic response to treadmill running. Ten, physically-active males aged 28 ± 4y (mean ±SD) completed two, counterbalanced, 8d trials. After 3d on a standardised diet, participants performed 60 min of treadmill running at 65% VO(2max) on Day 4 following an overnight fast (FAST) or a standardised breakfast (FED). Blood samples were collected at baseline, before and during exercise, for 3h after exercise, and on four consecutive follow-up days (FU1-FU4). Plasma/serum were analysed for the c-terminal telopeptide region of collagen type 1 (β-CTX), n-terminal propeptides of procollagen type 1 (P1NP), osteocalcin (OC), bone alkaline phosphatase (bone ALP), parathyroid hormone (PTH), albumin-adjusted calcium, phosphate, osteoprotegerin (OPG), cortisol, leptin and ghrelin. Only the β-CTX response was significantly affected by feeding. Pre-exercise concentrations decreased more in FED compared with FAST (47% vs 26%, P<0.001) but increased during exercise in both groups and were not significantly different from baseline at 1h post-exercise. At 3h post-exercise, concentrations were decreased (33%, P<0.001) from baseline in FAST and significantly lower (P<0.001) than in FED. P1NP and PTH increased, and OC decreased during exercise. Bone markers were not significantly different from baseline on FU1-FU4. Fasting had only a minor effect on the bone metabolic response to subsequent acute, endurance exercise, reducing the duration of the increase in β-CTX during early recovery, but having no effect on changes in bone formation markers. The reduced duration of the β-CTX response with fasting was not fully explained by changes in PTH, OPG, leptin or ghrelin.
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Amelio PD, Panico A, Spertino E, Isaia GC. Energy metabolism and the skeleton: Reciprocal interplay. World J Orthop 2012; 3:190-8. [PMID: 23330074 PMCID: PMC3547113 DOI: 10.5312/wjo.v3.i11.190] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2011] [Revised: 07/31/2012] [Accepted: 10/20/2012] [Indexed: 02/06/2023] Open
Abstract
The relation between bone remodelling and energy expenditure is an intriguing, and yet unexplained, challenge of the past ten years. In fact, it was only in the last few years that the skeleton was found to function, not only in its obvious roles of body support and protection, but also as an important part of the endocrine system. In particular, bone produces different hormones, like osteocalcin (OC), which influences energy expenditure in humans. The undercarboxylated form of OC has a reduced affinity for hydroxyapatite; hence it enters the systemic circulation more easily and exerts its metabolic functions for the proliferation of pancreatic β-cells, insulin secretion, sensitivity, and glucose tolerance. Leptin, a hormone synthesized by adipocytes, also has an effect on both bone remodelling and energy expenditure; in fact it inhibits appetite through hypothalamic influence and, in bone, stimulates osteoblastic differentiation and inhibits apoptosis. Leptin and serotonin exert opposite influences on bone mass accrual, but several features suggest that they might operate in the same pathway through a sympathetic tone. Serotonin, in fact, acts via two opposite pathways in controlling bone remodelling: central and peripheral. Serotonin product by the gastrointestinal tract (95%) augments bone formation by osteoblast, whereas brain-derived serotonin influences low bone mineral density and its decrease leads to an increase in bone resorption parameters. Finally, amylin (AMY) acts as a hormone that alters physiological responses related to feeding, and plays a role as a growth factor in bone. In vitro AMY stimulates the proliferation of osteoblasts, and osteoclast differentiation. Here we summarize the evidence that links energy expenditure and bone remodelling, with particular regard to humans.
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Nur H, Toraman NF, Arica Z, Sarier N, Samur A. The relationship between body composition and bone mineral density in postmenopausal Turkish women. Rheumatol Int 2012; 33:607-12. [PMID: 22481215 DOI: 10.1007/s00296-012-2391-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2011] [Accepted: 03/11/2012] [Indexed: 10/28/2022]
Abstract
In a retrospective cross-sectional study among 202 postmenopausal women aged 46-75 years, we aimed to investigate the relationship between body composition and bone mineral density (BMD) to determine whether fat mass or lean mass is a better determinant of BMD in Turkish postmenopausal women. Lumbar spine (L1-L4) and proximal femur BMD were measured by dual energy X-ray absorbsiometry. Body composition analysis was performed by bioelectric impedance method and fat mass, lean mass, and percent fat were measured. Both fat mass and lean mass were positively correlated with BMD at the lumbar spine and proximal femur, weight and body mass index. Lean mass was also positively correlated with height and negatively correlated with age and years since menopause (P < 0.01). The correlations of fat mass and lean mass with BMD at the lumbar spine and proximal femur remained significant after adjustment for age, years since menopause and height. When the lean mass was adjusted together with age, years since menopause and height, the significant relationship between the fat mass and BMD continued, however the significant correlation between the lean mass and BMD disappeared at all sites after adjustment for fat mass. In multiple regression analyses, fat mass was the significant determinant of all BMD sites. Our data suggest that fat mass is the significant determinant of BMD at the lumbar spine and proximal femur, and lean mass does not have an impact on BMD when fat mass was taken into account in Turkish postmenopausal women.
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Affiliation(s)
- Hakan Nur
- Department of Physical Medicine and Rehabilitation, Antalya Education and Research Hospital, Antalya, Turkey.
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Inhibition of Bone Loss by Cissus quadrangularis in Mice: A Preliminary Report. J Osteoporos 2012; 2012:101206. [PMID: 22779034 PMCID: PMC3388386 DOI: 10.1155/2012/101206] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2012] [Accepted: 04/26/2012] [Indexed: 11/18/2022] Open
Abstract
Women drastically loose bone during and after menopause leading to osteoporosis, a disease characterized by low bone mass increasing the risk of fractures with minor trauma. Existing therapies mainly reduce bone resorption, however, all existing drugs have severe side effects. Recently, the focus is to identify alternative medicines that can prevent and treat osteoporosis with minimal or no side effects. We used Cissus quadrangularis (CQ), a medicinal herb, to determine its effects on bone loss after ovariectomy in C57BL/6 mice. Two-month old mice were either sham operated or ovariectomized and fed CQ diet. After eleven weeks, mice were sacrificed and the long bones scanned using pQCT and μCT. In the distal femoral metaphysis, femoral diaphysis, and proximal tibia, control mice had decreased cancellous and cortical bone, while CQ-fed mice showed no significant differences in the trabecular number, thickness, and connectivity density, between Sham and OVX mice, except for cortical bone mineral content in the proximal tibia. There were no changes in the bone at the tibio-fibular junction between groups. We conclude that CQ effectively inhibited bone loss in the cancellous and cortical bones of femur and proximal tibia in these mice.
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Wang L, Tang X, Zhang H, Yuan J, Ding H, Wei Y. Elevated leptin expression in rat model of traumatic spinal cord injury and femoral fracture. J Spinal Cord Med 2011; 34:501-9. [PMID: 22118258 PMCID: PMC3184488 DOI: 10.1179/2045772311y.0000000034] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Abstract
BACKGROUND Few studies have reported a relationship between leptin induced by spinal cord injury (SCI) and healing bone tissue. OBJECTIVE To observe serum and callus leptin expression within the setting of fracture and traumatic SCI. METHODS Seventy-two male Sprague Dawley rats were randomized equally into four groups: control, SCI group, fracture group, and fracture/SCI group. Rats were sacrificed at 7, 14, 21, and 28 days post-fracture/SCI. Serum leptin was detected using radioimmunoassay at 1, 7, 14, 21, and 28 days, and callus formation was measured radiologically at 14, 21, and 28 days. Callus leptin was analyzed by means of immunohistochemistry. RESULTS Serum leptin in the fracture group, SCI group, and combined fracture/SCI group were all significantly increased compared to control group at the 1, 7, 14, and 2-day time points (P < 0.05). Serum leptin in the combined fracture/SCI group was significantly higher than in the fracture group at 7, 14, and 21 days (P < 0.05), and higher than in SCI groups at 14 and 21days after operation (P < 0.05). The percentage of leptin-positive cells in the fracture/SCI callus, and callus volume was significantly higher than in the fracture-only group (P < 0.001). CONCLUSIONS Overall, elevated leptin expression was demonstrated within healing bone especially in the 21 days of a rat model combining fracture and SCI. A close association exists between leptin levels and the degree of callus formation in fractures.
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Affiliation(s)
- Lei Wang
- Department of Orthopedics, The Affiliated People's Hospital with Jiangsu University, Zhenjiang, Jiangsu Province, China
| | - Xingguo Tang
- Department of Orthopedics, The Affiliated People's Hospital with Jiangsu University, Zhenjiang, Jiangsu Province, China
| | - Hongxi Zhang
- Department of Orthopedics, The Affiliated People's Hospital with Jiangsu University, Zhenjiang, Jiangsu Province, China,Correspondence to: Hongxi Zhang, Dianli Road 8, Zhenjiang 212001, Jiangsu Province, China.
| | - Jishan Yuan
- Department of Orthopedics, The Affiliated People's Hospital with Jiangsu University, Zhenjiang, Jiangsu Province, China
| | - Hua Ding
- Department of Orthopedics, The Affiliated People's Hospital with Jiangsu University, Zhenjiang, Jiangsu Province, China
| | - Yongzhong Wei
- Department of Orthopedics, The First Affiliated Hospital with Nanjing University, Jiangsu Province, China
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Conroy R, Girotra M, Shane E, McMahon DJ, Pavlovich KH, Leibel RL, Rosenbaum M, Korner J. Leptin administration does not prevent the bone mineral metabolism changes induced by weight loss. Metabolism 2011; 60:1222-6. [PMID: 21489573 PMCID: PMC3139754 DOI: 10.1016/j.metabol.2011.02.010] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2010] [Revised: 02/10/2011] [Accepted: 02/18/2011] [Indexed: 01/19/2023]
Abstract
The objective was to examine the effects of weight loss and leptin administration following weight loss on calciotropic hormones and bone turnover. This was a prospective, single-blinded study of 12 subjects (8 women, 4 men; 2 nonobese, 10 obese; age range, 19-46 years) who were studied on an inpatient basis while maintaining their usual weight [Wt(initial)] and during maintenance of 10% weight loss while receiving twice-daily injections of either a placebo [Wt(-10%P)] or replacement doses of leptin [Wt(-10%L)]. The main outcome measures were markers of bone formation (bone alkaline phosphatase and procollagen type 1 amino terminal propeptide) and resorption (N-telopeptide) as well as parathyroid hormone, calcium, and 25-hydroxy vitamin D measured from fasting morning serum. As expected, serum leptin declined with weight loss. Bone alkaline phosphatase decreased by 12.3% ± 3.9% between Wt(initial) and Wt(-10%P) and remained suppressed after leptin administration (both P < .01 compared with baseline). N-telopeptides increased by 37.2% ± 11.3% from Wt(initial) to Wt(-10%L) (P < .01). Procollagen type 1 amino terminal propeptide, parathyroid hormone, calcium, and 25-hydroxy vitamin D did not change. These results suggest that both decreased bone formation and increased bone resorption underlie bone loss associated with weight loss. Leptin administration did not prevent the uncoupling of bone remodeling that accompanies weight loss.
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Affiliation(s)
| | - Monica Girotra
- Columbia University College of Physicians and Surgeons, Department of Medicine, New York, New York 10032
| | - Elizabeth Shane
- Columbia University College of Physicians and Surgeons, Department of Medicine, New York, New York 10032
| | - Donald J. McMahon
- Columbia University College of Physicians and Surgeons, Department of Medicine, New York, New York 10032
| | | | | | | | - Judith Korner
- Columbia University College of Physicians and Surgeons, Department of Medicine, New York, New York 10032
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Gordon CM. Leptin and the skeleton-where is the fat? Metabolism 2011; 60:1203-6. [PMID: 21742353 DOI: 10.1016/j.metabol.2011.05.020] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2011] [Revised: 05/23/2011] [Accepted: 05/23/2011] [Indexed: 11/20/2022]
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Migliaccio S, Greco EA, Fornari R, Donini LM, Lenzi A. Is obesity in women protective against osteoporosis? Diabetes Metab Syndr Obes 2011; 4:273-82. [PMID: 21792326 PMCID: PMC3139535 DOI: 10.2147/dmso.s11920] [Citation(s) in RCA: 81] [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: 07/02/2011] [Indexed: 12/11/2022] Open
Abstract
The belief that obesity is protective against osteoporosis has recently come into question. The latest epidemiologic and clinical studies have shown that a high level of fat mass might be a risk factor for osteoporosis and fragility fractures. Further, increasing evidence seems to indicate that different components of the metabolic syndrome, ie, hypertension, increased triglycerides, reduced high-density lipoprotein cholesterol, are also potential risk factors for the development of low bone mineral density and osteoporosis. This review considers both the older and more recent data in the literature in order to evaluate further the relationship between fat tissue and bone tissue.
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Affiliation(s)
- Silvia Migliaccio
- Dipartimento di Medicina Sperimentale, Sezione di Fisiopatologia, Endocrinologia e Nutrizione, Università Sapienza di Roma
- Dipartimento di Scienze della Salute, Università Foro Italico di Roma, Italia
| | - Emanuela A Greco
- Dipartimento di Medicina Sperimentale, Sezione di Fisiopatologia, Endocrinologia e Nutrizione, Università Sapienza di Roma
| | - Rachele Fornari
- Dipartimento di Medicina Sperimentale, Sezione di Fisiopatologia, Endocrinologia e Nutrizione, Università Sapienza di Roma
| | - Lorenzo M Donini
- Dipartimento di Medicina Sperimentale, Sezione di Fisiopatologia, Endocrinologia e Nutrizione, Università Sapienza di Roma
| | - Andrea Lenzi
- Dipartimento di Medicina Sperimentale, Sezione di Fisiopatologia, Endocrinologia e Nutrizione, Università Sapienza di Roma
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Clempson A, Pollott G, Brickell J, Bourne N, Munce N, Wathes D. Evidence that leptin genotype is associated with fertility, growth, and milk production in Holstein cows. J Dairy Sci 2011; 94:3618-28. [DOI: 10.3168/jds.2010-3626] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2010] [Accepted: 03/10/2011] [Indexed: 01/30/2023]
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Um S, Choi JR, Lee JH, Zhang Q, Seo BM. Effect of leptin on differentiation of human dental stem cells. Oral Dis 2011; 17:662-9. [DOI: 10.1111/j.1601-0825.2011.01820.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Pobeha P, Ukropec J, Skyba P, Ukropcova B, Joppa P, Kurdiova T, Javorsky M, Klimes I, Tkac I, Gasperikova D, Tkacova R. Relationship between osteoporosis and adipose tissue leptin and osteoprotegerin in patients with chronic obstructive pulmonary disease. Bone 2011; 48:1008-14. [PMID: 21376149 DOI: 10.1016/j.bone.2011.02.017] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2010] [Revised: 02/18/2011] [Accepted: 02/19/2011] [Indexed: 10/18/2022]
Abstract
INTRODUCTION The role of fat-bone interactions in the pathogenesis of osteoporosis in chronic obstructive pulmonary disease (COPD) is poorly understood. Our aim was to investigate expressions of leptin and osteoprotegerin (OPG) in the adipose tissue, and their relationships to osteoporosis in patients with COPD. METHODS In 39 patients with stable COPD, bone mineral density (BMD) and body composition was assessed by Dual Energy X-Ray Absorptiometry. Serum leptin was determined by the enzyme-linked immunosorbent assay, and bone turnover markers osteocalcin and β-crosslaps by the electrochemiluminiscence immunoassays. Subcutaneous adipose tissue samples were analyzed using real-time PCR. RESULTS Twenty-one patients without, and 18 with osteoporosis were enrolled (35 men; age 62.2 ± 7.3years). Compared to patients without osteoporosis, those with the disease had significantly lower serum levels and adipose tissue expressions of leptin, in association with increased serum β-crosslaps (p=0.028, p=0.034, p=0.022, respectively). Log adipose tissue leptin was inversely related to serum β-crosslaps (p=0.015), and directly to serum leptin (p<0.001) and to the total, femoral, and lumbar BMD and T-score (p<0.02 for all relationships). Adipose tissue OPG expression was related to all variables of bone density except for lumbar BMD and T-score (p<0.05 for all relationships). Log adipose tissue leptin and OPG expressions predicted femoral T-score independently of age, gender and pulmonary function (p<0.001, adjusted R(2)=0.383; p=0.008, adjusted R(2)=0.301, respectively). Introducing body mass (or fat mass) index into these models eliminated independent predictive value of leptin and OPG expressions. CONCLUSION Our results suggest that adipose tissue leptin and OPG expressions are related to osteoporosis in patients with COPD, and appear to act as mediators between fat mass and BMD.
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Affiliation(s)
- Pavol Pobeha
- Department of Respiratory Medicine, and Tuberculosis, P.J. Safarik University, Kosice, Slovakia
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Horner KC, Troadec JD, Blanchard MP, Dallaporta M, Pio J. Receptors for leptin in the otic labyrinth and the cochlear-vestibular nerve of guinea pig are modified in hormone-induced anorexia. Hear Res 2010; 270:48-55. [PMID: 20875846 DOI: 10.1016/j.heares.2010.09.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2010] [Revised: 09/20/2010] [Accepted: 09/22/2010] [Indexed: 01/13/2023]
Abstract
Metabolic syndromic inner ear pathology is a recognized condition in clinical practice but the possible causes remain controversial. We have previously reported that chronically-implanted estrogen implants in guinea pig results in hyperprolactinemia and hearing loss together with otic bone dysmorphology. The animals also present with anorexia. The hormone leptin has major roles in the regulation of satiety as well as bone metabolism and so we hypothesized that leptin might contribute to pathology of the otic labyrinth. We employed immunohistochemistry to investigate leptin receptor (ObR) expression. In control animals, ObR immunolabeling was not detected in the bone of the otic capsule but immunolabeling was observed in the cochlear-vestibular nerve. The labeling was associated with the astrocytic glial dome area, which marks the transition between central and peripheral parts of the nerve. In estrogen-treated animals, positive-ObR immunolabeling was observed in osteoblasts in new bone of the otic capsule and the ObR labeling was reduced in the cochlear-vestibular nerve compared to controls. The data provide evidence that leptin may target the labyrinth - affecting the bone and the nerve - and so could contribute to ongoing protection of the inner ear. Leptin disturbance might contribute to metabolic syndromes involving the audiovestibular system.
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Affiliation(s)
- Kathleen C Horner
- CRN2M-Dept Physiologie Neurovégétative, Université Paul Cézanne, Faculté des Sciences et Techniques, Avenue Escadrille Normandie-Niémen, 13397 Marseille Cedex 20, France.
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Kapur S, Amoui M, Kesavan C, Wang X, Mohan S, Baylink DJ, Lau KHW. Leptin receptor (Lepr) is a negative modulator of bone mechanosensitivity and genetic variations in Lepr may contribute to the differential osteogenic response to mechanical stimulation in the C57BL/6J and C3H/HeJ pair of mouse strains. J Biol Chem 2010; 285:37607-18. [PMID: 20851886 PMCID: PMC2988366 DOI: 10.1074/jbc.m110.169714] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
This study investigated the role of leptin receptor (Lepr) signaling in determining the bone mechanosensitivity and also evaluated whether differences in the Lepr signaling may contribute to the differential osteogenic response of the C57BL/6J (B6) and C3H/HeJ (C3H) pair of mouse strains to mechanical stimuli. This study shows that a loading strain of ∼2,500 με, which was insufficient to produce a bone formation response in B6 mice, significantly increased bone formation parameters in leptin-deficient ob(-)/ob(-) mice and that a loading strain of ∼3,000 με also yielded greater osteogenic responses in Lepr-deficient db(-)/db(-) mice than in wild-type littermates. In vitro, a 30-min steady shear stress increased [(3)H]thymidine incorporation and Erk1/2 phosphorylation in ob(-)/ob(-) osteoblasts and db(-)/db(-) osteoblasts much greater than those in corresponding wild-type osteoblasts. The siRNA-mediated suppression of Lepr expression in B6 osteoblasts enhanced (but in osteoblasts of C3H (the mouse strain with poor bone mechanosensitivity) restored) their anabolic responses to shear stress. The Lepr signaling (leptin-induced Jak2/Stat3 phosphorylation) in C3H osteoblasts was higher than that in B6 osteoblasts. One of the three single nucleotide polymorphisms in the C3H Lepr coding region yielded an I359V substitution near the leptin binding region, suggesting that genetic variation of Lepr may contribute to a dysfunctional Lepr signaling in C3H osteoblasts. In conclusion, Lepr signaling is a negative modulator of bone mechanosensitivity. Genetic variations in Lepr, which result in a dysfunctional Lepr signaling in C3H mice, may contribute to the poor osteogenic response to loading in C3H mice.
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Affiliation(s)
- Sonia Kapur
- Musculoskeletal Disease Center, Jerry L Pettis Memorial Veterans Affairs Medical Center, Loma Linda, California 92357, USA
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Ahmed HM, El-Shereef HK, El-Gendi SS, El-Sherif WT, Bakheet MY, Galal GM, Abdel-Wahab SH, El-Moneum OA. Leptin, osteocalcin, and bone mineral density in post-hepatitic liver cirrhosis. Arab J Gastroenterol 2010. [DOI: 10.1016/j.ajg.2010.07.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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