雌激素缺乏条件下MiR-133通过调控间充质干细胞成骨分化参与骨质疏松形成的机制

MiR-133 is involved in estrogen deficiency induced osteoporosis by modulating osteogenic differentiation of mesenchymal stem cell

目的探究MiR-133在雌激素缺乏条件下在骨质疏松中的表达情况及对间充质干细胞成骨分化的影响。方法从绝经后骨质疏松患者处分离间充质干细胞,利用qRT-PCR检测MiR-133的mRNA表达水平;利用荧光素酶和Western印迹检测MiR-133对其靶基因SLC39A1表达的调控;通过检测碱性磷酸酶和RUNX2表达情况,显示MiR-133和SLC39A1对间充质干细胞成骨分化产生的影响。结果 MiR-133在雌激素缺乏的患者中显著升高,并且负性调控间充质干细胞成骨分化能力;MiR-133直接靶向负性调控SLC39A1启动子活性,降低SLC39A1的蛋白表达水平;SLC39A1能够上调碱性磷酸酶的活性,上调RUNX2的表达水平。结论 MiR-133的过表达与雌激素缺乏具有显著相关性,MiR-133通过抑制SLC39A1的表达弱化间充质干细胞成骨分化能力,进而促使绝经后骨质疏松的发生。

Objective To investigate the relationships among MiR-133（ estrogen deficiency induced osteoporosis and osteogenic differentiation of mesenchymal stem cells）. Methods The osteogenic differentiation of mesenchymal stem cells ability of miR-133 on h MSC cells was detected by qRT-PCR. The binding between miR-133 and predicted target SLC39A1 were verified by dual luciferase assay and Western blot analysis. RUNX2 related proteins were detected using Western blot. Results miR-133 expression was significantly enhanced as a result of estrogen deficiency. Its overexpression was negatively correlated to osteogenic differentiation of h MSCs. SLC39A1 showed an inverse expression trend to miR-133 during the differentiation. Western blot test showed osteogenic differentiation of mesenchymal stem cells related proteins RUNX2 were obvious changed. Conclusions miR-133 overexpression is associated with estrogen deficiency. MiR-133 could induce postmenopausal osteoporosis by weakening osteogenic differentiation of h MSCs,at least partly through repressing SLC39A1 expression.