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GLP-1 promotes osteogenic differentiation of human ADSCs via the Wnt/GSK-3β/β-catenin pathway.
Molecular and Cellular Endocrinology ( IF 3.8 ) Pub Date : 2020-06-29 , DOI: 10.1016/j.mce.2020.110921
Yun Li 1 , Huirong Fu 2 , Hou Wang 2 , Shunkui Luo 2 , Lingling Wang 2 , Jiandi Chen 2 , Hongyun Lu 3
Affiliation  

Glucagon-like peptide-1 (GLP-1) analogues are promising anti-diabetic drugs which had been shown to have beneficial effects on bone metabolism in clinical practice, but the molecular mechanism remains unclear. In this study, we evaluated whether GLP-1 can affect the “intestine-fat-bone axis” via the Wnt/GSK-3β/β-catenin pathway. We established a diabetic mouse model and then treated mice with GLP-1 analogue liraglutide. The results showed that after liraglutide treatment, glucose tolerance and insulin tolerance were significantly improved in diabetic mice as expected. Moreover, osteogenic markers such as collagenⅠ, Runx2 and OCN were upregulated; and the adipogenic differentiation markers C/EBP-α and PPAR-γ were downregulated, these results indicated that liraglutide could ameliorate the osteogenic metabolism in diabetic mice. In the cell model, human ADSCs (hADSCs) were cultured and induced to undergo osteogenic and adipogenic differentiation under high glucose conditions in vitro and then treated with GLP-1. The results showed that GLP-1 repressed the induction of adipocyte differentiation biomarkers and the secretion of GSK-3β in a dose-dependent manner. In addition, GLP-1 enhanced the expression of osteoblastogenic biomarkers, such as OCN, Runx2 and collagenⅠ, and promoted osteoblastic mineralization. These effects were substantially suppressed by the Wnt signal recombinant human DKK-1 or activated by Wnt pathway agonist LiCl. Silencing of GSK-3β showed that the levels of β-catenin, GSK-3β and Runx2 were significantly increased by 2.46-, 2.05-, 4.44-fold after GLP-1 treatment compared to that observed in the GSK-3β lentiviral group, respectively. We conclude that GLP-1 promotes the osteogenic differentiation of hADSCs via the Wnt/GSK-3β/β-catenin pathway.



中文翻译:

GLP-1通过Wnt /GSK-3β/β-catenin途径促进人ADSC的成骨分化。

胰高血糖素样肽-1(GLP-1)类似物是有前途的抗糖尿病药物,在临床实践中已显示对骨代谢具有有益作用,但分子机制尚不清楚。在这项研究中,我们评估了GLP-1是否可以通过以下途径影响“肠脂骨轴”Wnt /GSK-3β/β-catenin途径。我们建立了糖尿病小鼠模型,然后用GLP-1类似物利拉鲁肽治疗小鼠。结果表明,利拉鲁肽治疗后,糖尿病小鼠的葡萄糖耐量和胰岛素耐量显着改善。此外,成骨标志物如Ⅰ型胶原,Runx2和OCN被上调。脂肪诱导分化标志物C /EBP-α和PPAR-γ被下调,表明利拉鲁肽可改善糖尿病小鼠的成骨代谢。在细胞模型中,人脂肪干细胞(hADSCs)中培养,并诱导高葡萄糖条件下经历成骨和成脂分化的体外然后用GLP-1处理 结果表明,GLP-1以剂量依赖的方式抑制脂肪细胞分化生物标志物的诱导和GSK-3β的分泌。另外,GLP-1增强了成骨细胞生物标志物如OCN,Runx2和胶原Ⅰ的表达,并促进了成骨细胞的矿化作用。这些作用被Wnt信号重组人DKK-1基本上抑制或被Wnt途径激动剂LiCl激活。GSK-3β沉默显示,与GSK-3β慢病毒组相比,GLP-1处理后,β-catenin,GSK-3β和Runx2的水平分别显着提高了2.46-,2.05-,4.44倍。 。我们得出结论,GLP-1通过Wnt /GSK-3β/β-catenin途径促进hADSCs的成骨分化。

更新日期:2020-07-22
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