Systemic leptin administration alters callus VEGF levels and enhances bone fracture healing in wildtype and ob/ob mice |
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| Institution: | 1. Department of Orthopedics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China;2. Department of General Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China;3. School of Pharmacy, Curtin University, Bentley, Australia;1. Flinders Medical Centre, Flinders Drive, Bedford Park, SA5042, Australia;2. Flinders University, Flinders Drive, Bedford Park, SA, 5042, Australia;3. University of Amsterdam, 1012 XW, Amsterdam, The Netherlands;1. Southmead Hospital, Bristol, UK;2. University Hospital Coventry and Warwickshire, Coventry, UK;3. Oxford University Hospitals, Oxford, UK;4. Sheffield Northern General Hospital, Sheffield, UK;5. University of the West of England, Bristol, UK;1. Trauma & Orthopaedics, St George’s University Hospitals NHS Foundation Trust, London, SW17 0QT, United Kingdom;2. Department of Radiology, St George’s University Hospitals NHS Foundation Trust, London, SW17 0QT, United Kingdom;1. Department of Occupational Therapy and Physiotherapy, Aalborg University Hospital, Aalborg, Denmark;2. Department of Orthopaedic Surgery, Aalborg University Hospital, Aalborg, Denmark;1. KU Leuven – University of Leuven, Faculty of Medicine, B-3000 Leuven, Belgium;2. University Hospitals Leuven, Department of Trauma Surgery, B-3000 Leuven, Belgium;3. KU Leuven – University of Leuven, Department of Development and Regeneration, B-3000 Leuven, Belgium;1. Department of Orthopaedic Surgery, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea;2. Department of Orthopaedic Surgery, Pusan National University Hospital, Busan, Republic of Korea |
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| Abstract: | IntroductionLeptin?s role in bone formation has been reported, however, its mechanism of affecting bone metabolism is remaining unclear. In this study, we aimed to test whether leptin has a positive effect on fracture healing through the possible mechanism of increasing vascular endothelial growth factor (VEGF) expression in callus tissue.MethodsStandardized femur fractures were created in leptin-deficient ob/ob and wildtype C57BL/6J mice, and recombinant mouse leptin or its vehicle (physiological saline) was administered intraperitoneally during the study. Body weight, radiological, histologic and immunoblotting analyses were performed at different stages of fracture healing.Key findingsThe results showed that leptin treatment led to lower rate of body weight change in both mice genotypes. Radiological and histological analyses showed that the experimental groups had better fracture healing at 14, 21 and 28 days compared to the control groups. Leptin-treated groups had signi?cantly higher VEGF expression in callus compared with the control groups at 2 and 3 weeks post-fracture except normal mice at 2 weeks, and leptin-deficient mice had higher VEGF levels in calluses than normal mice at the same timepoint.ConclusionLow-dose systemically-administered leptin has a positive effect on promoting fracture healing during the latter stages in a clinically-relevant mouse bone fracture model, and increase callus VEGF levels. |
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| Keywords: | Callus Fracture Leptin VEGF Bone healing |
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