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Dapagliflozin and Liraglutide Therapies Rapidly Enhanced Bone Material Properties and Matrix Biomechanics at Bone Formation Site in a Type 2 Diabetic Mouse Model.
Calcified Tissue International ( IF 4.2 ) Pub Date : 2020-07-08 , DOI: 10.1007/s00223-020-00720-4
Aleksandra Mieczkowska 1 , Paul Millar 2 , Daniel Chappard 1, 3, 4 , Victor A Gault 2 , Guillaume Mabilleau 1, 3, 4
Affiliation  

The aim of this study is to compare head-to-head the effects of dapagliflozin and liraglutide on bone strength and bone material properties in a pre-clinical model of diabetes-obesity. Combined low-dose streptozotocin and high fat feeding were employed in mice to promote obesity, insulin resistance, and hyperglycaemia. Mice were administered daily for 28 days with saline vehicle, 1 mg/kg dapagliflozin or 25 nmol/kg liraglutide. Bone strength was assessed by three-point bending and nanoindentation. Bone material properties were investigated by Fourier transform infrared microspectroscopy/imaging. Although diabetic controls presented with dramatic reductions in mechanical strength, no deterioration of bone microarchitecture was apparent. At the tissue level, significant alterations in phosphate/amide ratio, carbonate/phosphate ratio, tissue water content, crystal size index, collagen maturity and collagen glycation were observed and linked to alteration of matrix biomechanics. Dapagliflozin and liraglutide failed to improve bone strength by 3-point bending or bone microarchitecture during the 28-day-treatment period. At bone formation site, dapagliflozin enhanced phosphate/amide ratio, mineral maturity, and reduced tissue water content, crystal size index, and collagen glycation. Liraglutide had significant effects on phosphate/amide ratio, tissue water content, crystal size index, mature collagen crosslinks, collagen maturity, and collagen glycation. At bone formation site, both drugs modulated matrix biomechanics. This study highlighted that these two molecules are effective in improving bone material properties and modulating matrix biomechanics at bone formation site. This study also highlighted that the resulting effects on bone material properties are not identical between dapagliflozin and liraglutide and not only mediated by lower blood glucose.



中文翻译:

Dapagliflozin和Liraglutide治疗在2型糖尿病小鼠模型中的骨骼形成部位迅速增强了骨骼的材料特性和基质生物力学。

这项研究的目的是在糖尿病肥胖的临床前模型中比较达格列净和利拉鲁肽对骨强度和骨材料特性的影响。低剂量链脲佐菌素和高脂喂养相结合,可促进小鼠肥胖,胰岛素抵抗和高血糖症。每天将小鼠用生理盐水,1 mg / kg达格列净或25 nmol / kg利拉鲁肽给药。通过三点弯曲和纳米压痕评估骨强度。通过傅立叶变换红外光谱/成像研究骨材料的性能。尽管糖尿病对照组的机械强度显着降低,但骨微结构没有明显恶化。在组织水平,磷酸盐/酰胺比,碳酸盐/磷酸盐比,观察组织水含量,晶体大小指数,胶原蛋白成熟度和胶原蛋白糖基化,并与基质生物力学的改变有关。在28天的治疗期间,达格列净和利拉鲁肽未能通过3点弯曲或骨骼微结构改善骨骼强度。在骨形成部位,达格列净增强磷酸盐/酰胺比,矿物质成熟度,并降低组织含水量,晶体尺寸指数和胶原糖基化。利拉鲁肽对磷酸盐/酰胺比,组织含水量,晶体尺寸指数,成熟的胶原交联,胶原成熟度和胶原糖基化有显着影响。在骨形成部位,两种药物均调节基质生物力学。这项研究强调了这两个分子可有效改善骨骼形成部位的骨骼材料特性和调节基质生物力学。

更新日期:2020-07-08
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