MiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling
Publication in refereed journal


摘要Osteogenic differentiation of mesenchymal stem cells (MSCs) is a complex process, which is regulated by various factors including microRNAs. Our preliminary data showed that the expression of endogenous miR-20a was increased during the course of osteogenic differentiation. Simultaneously, the expression of osteoblast markers and regulators BMP2, BMP4, Runx2, Osx, OCN and OPN was also elevated whereas adipocyte markers PPAR gamma and osteoblast antagonist, Bambi and Crim1, were downregulated, thereby suggesting that miR-20a plays an important role in regulating osteoblast differentiation. To validate this hypothesis, we tested its effects on osteogenic differentiation by introducing miR-20a mimics and lentiviral-miR20a-expression vectors into hMSCs. We showed that miR-20a promoted osteogenic differentiation by the upregulation of BMP/Runx2 signaling. We performed bioinformatics analysis and predicted that PPAR gamma, Bambi and Crim1 would be potential targets of miR-20a. PPAR gamma is a negative regulator of BMP/Runx2 signaling whereas Bambi or Crim1 are antagonists of the BMP pathway. Furthermore, we confirmed that all these molecules were indeed the targets of miR-20a by luciferase reporter, quantitative RT-PCR and western blot assays. Similarly to miR-20a overexpression, the osteogenesis was enhanced by the silence of PPAR gamma, Bambi or Crim1 by specific siRNAs. Taken together, for the first time, we demonstrated that miR-20a promoted the osteogenesis of hMSCs in a co-regulatory pattern by targeting PPAR gamma, Bambi and Crim1, the negative regulators of BMP signaling.
著者Zhang JF, Fu WM, He ML, Xie WD, Lv Q, Wan G, Li G, Wang H, Lu G, Hu X, Jiang S, Li JN, Lin MCM, Zhang YO, Kung HF
期刊名稱RNA Biology
詳細描述To ORKTS: duplicated record
出版社Taylor & Francis: STM, Behavioural Science and Public Health Titles
頁次829 - 838
關鍵詞BMP signaling pathway; co-regulatory pattern; mesenchymal stem cell; miR-20a; osteogenic differentiation
Web of Science 學科類別Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY

上次更新時間 2020-24-11 於 00:18