目的:探讨组蛋白去乙酰化酶抑制剂丁酸钠(sodium butyrate,NaBu)对脂肪间充质干细胞(adipose tissue—derived stem cells,ADSCs)向成骨细胞分化的影响及其机制。方法:将培养至第3代的大鼠ADSCs分为2组,NaBu组与阴性对照组。ADSCs经NaBu处理72小时后加入成骨培养基进行诱导分化,以Real—timeRT—PCR检测Runx2 mRNA表达。ChIP结合Real—timeRT—PCR检测Runx2基因启动子区甲基化水平及组蛋白修饰水平。结果:与阴性对照组相比。NaBu促使ADSCs中的Runx2和OCN表达增加及Runx2启动子区域乙酰化H3K9募集增加,有效提高ADSCs成骨分化能力。结论:NaBu通过改变Runx2基因启动子区域组蛋白乙酰化修饰促进脂肪间充质干细胞向成骨细胞分化。
Objective To investigate the effects of histone deacetylase inhibitor sodium butyrate (NaBu)on the osteogenic differentiation of adipose tissue-derived stem cells (ADSCs)in vitro in rat. Methods Bone marrow mesenchymal stem cells of rat were isolated, cultured and identified. The cells of second passage were divided into 2 groups: sodium butyrate group and control group. The cultured ADSCs at 80% confluence were induced by osteogenic differentiation medium with or without NaBu treatment for the first 3 days. The expression of bone specific genes and histone modifications of Runx2 promoter were detected. Results Compared with the control group, the expressions of Runx2 and OCN in ADSCs and recruitment of acetylated H3K9 in Runx2 promoter region increased in sodium butyrate group. Conclusion Histone deacetylase inhibitor sodium butyrate promotes the osteogenic differentiation of rats' adipose-derived stem cells by altering the epigenetic modifications on Runx2 promoter.