Exendin-4促进小鼠脂肪干细胞向成骨细胞分化
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摘要
目的探讨艾塞那肽-4(exendin-4)能否促进脂肪干细胞向成骨细胞分化及分子机制。方法体外培养鉴定脂肪干细胞,通过脂肪干细胞的多向分化能力验证脂肪干细胞。给予脂肪干细胞exendin-4刺激,观察成骨相关基因蛋白的表达。结果 Exendin-4诱导脂肪干细胞向成骨细胞分化抑制向脂肪细胞分化。不仅如此,exendin-4可能通过提高PI3K、 Akt和β-catenin的表达促进脂肪干细胞(ADSCs)向成骨细胞分化。结论 Exendin-4促进小鼠脂肪干细胞(ADSCs)向成骨细胞分化,可能是通过激活GLP-1R通路。
Objective To determine the effect of exendin-4 on the differentiation of mouse ADSCs to osteoblasts and the mechanisms. Methods The ADSCs were isolated and characterized by osteoblastogenesis and osteoclastogenesis. Besides, the effect of exendin-4 on osteoblasts differentiation and the mechanisms was examined.Results Exendin-4 promoted osteoblasts differentiation and inhibited adipocytes differentiation. Furthermore, exendin-4 promoted osteoblastogenesis probably through PI3 K-Akt signaling pathway and Wnt signaling pathway.Conclusions Exendin-4 promotes ADSCs differentiation to osteoblasts. The osteogenesis is probably through GLP-1 R signaling pathway.
Objective To determine the effect of exendin-4 on the differentiation of mouse ADSCs to osteoblasts and the mechanisms. Methods The ADSCs were isolated and characterized by osteoblastogenesis and osteoclastogenesis. Besides, the effect of exendin-4 on osteoblasts differentiation and the mechanisms was examined.Results Exendin-4 promoted osteoblasts differentiation and inhibited adipocytes differentiation. Furthermore, exendin-4 promoted osteoblastogenesis probably through PI3 K-Akt signaling pathway and Wnt signaling pathway.Conclusions Exendin-4 promotes ADSCs differentiation to osteoblasts. The osteogenesis is probably through GLP-1 R signaling pathway.
引文
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[3] Ma X,Meng J,Jia M,et al.exendin-4,a glucagon-like peptide-1 receptor agonist,prevents osteopenia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats[J].Bone Miner Res,2013,28:1641-1652.
[4] Li R,Xu W,Luo S,et al.Effect of exenatide,insulin and pioglitazone on bone metabolism in patients with newly diagnosed type 2 diabetes[J].Acta Diabetol,2015,52:1083-1091.
[5] Nuche-Berenguer B,Moreno P,Esbrit P,et al.Effect of GLP-1 treatment on bone turnover in normal,type 2 diabetic,and insulin-resistant states[J].Calcif Tissue Int,2009,84:453-461.
[6] DeFronzo RA,Ratner RE,Han J,et al.Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes[J].Diabetes Care,2005,28:1092-1100.
[7] Zhou H,Li D,Shi C,et al.Effects of exendin-4 on bone marrow mesenchymal stem cell proliferation,migration and apoptosis in vitro[J].Sci Rep,2015,5:12898.doi:10.1038/srep12898.
[8] Nejad-Dehbashi F,Hashemitabar M,Orazizadeh M,et al.The effects of exendine-4 on insulin producing cell differentiation from rat bone marrow-derived mesenchymal stem cells[J].Cell J,2014,16:187-194.
[9] Iepsen EW,Lundgren JR,Hartmann B,et al.GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women[J].J Clin Endocrinol Metab,2015,100:2909-2917.
[10] Qing X,Wei W,Jing R,et al.Effects of miR-146a on the osteogenesis of adipose-derived mesenchymal Stem cells and bone regeneration[J].Sci Rep,2017,7:42840.doi:10.1038/srep42840.