Mansur Sity Aishah, Mieczkowska Aleksandra, Flatt Peter R, Chappard Daniel, Irwin Nigel, Mabilleau Guillaume
School of Biomedical Sciences, University of Ulster, Coleraine, United Kingdom.
Groupe études remodelage osseux et biomatériaux, GEROM, SFR 42-08, Université d'Angers, Institut de Biologie en Santé, CHU d'Angers, Angers, France.
Front Endocrinol (Lausanne). 2019 Feb 12;10:51. doi: 10.3389/fendo.2019.00051. eCollection 2019.
Type 2 diabetes mellitus (T2DM) has recently been recognized as a significant risk factor for bone fragility. Careful investigations of bone mechanical properties in human studies suggested possible alterations of bone composition, although this axis has poorly been investigated. The main aim of this study was to evaluate the impact of high fat diet-induced diabetes and therapy using the clinically approved GLP-1 receptor agonist, exenatide, on tissue bone mechanical properties and compositional parameters. Male mice had free access to high fat diet for 16 weeks to induce diabetes prior to commencement of the study. Exenatide was administered twice daily by i.p. injection at a dose of 25 nmol/kg for 52 days. Normal and high fat diet fed (HFD) mice injected with saline were used as controls. Bone mechanical properties was assessed at the organ level by 3-point bending and at the tissue level by nanoindentation. Bone microarchitecture was investigated by microcomputed tomography and bone composition was evaluated by Fourier transform infrared imaging. HFD mice exhibited profound alterations of bone mechanical properties at both the organ and tissue level. Collagen maturity as well as trabecular and cortical bone microarchitectures were abnormal. Administration of exenatide, led to clear ameliorations in bone mechanical properties at the organ and tissue levels by modifications of both cortical microarchitecture and bone compositional parameters (collagen maturity, mineral crystallinity, carbonate/phosphate ratio, acid phosphate content). These results bring new light on the mode of action of exenatide in bone physiology and demonstrate the value of GLP-1 mimetics in the treatment of fragility fractures in diabetes.
2型糖尿病（T2DM）最近被认为是导致骨脆性的一个重要风险因素。人体研究中对骨力学性能的仔细调查表明骨成分可能发生改变，尽管这方面的研究还很欠缺。本研究的主要目的是评估高脂饮食诱导的糖尿病以及使用临床批准的胰高血糖素样肽-1（GLP-1）受体激动剂艾塞那肽进行治疗，对组织骨力学性能和成分参数的影响。在研究开始前，雄性小鼠自由进食高脂饮食16周以诱导糖尿病。通过腹腔注射，以25 nmol/kg的剂量每日两次给予艾塞那肽，持续52天。注射生理盐水的正常饮食和高脂饮食（HFD）小鼠用作对照。通过三点弯曲在器官水平评估骨力学性能，通过纳米压痕在组织水平评估。通过微型计算机断层扫描研究骨微结构，通过傅里叶变换红外成像评估骨成分。HFD小鼠在器官和组织水平均表现出骨力学性能的显著改变。胶原蛋白成熟度以及小梁骨和皮质骨微结构均异常。给予艾塞那肽后，通过改变皮质微结构和骨成分参数（胶原蛋白成熟度、矿物质结晶度、碳酸盐/磷酸盐比率、酸性磷酸酶含量），在器官和组织水平上明显改善了骨力学性能。这些结果为艾塞那肽在骨生理学中的作用方式带来了新的认识，并证明了GLP-1模拟物在治疗糖尿病性脆性骨折中的价值。
