Promotion Effects of miR-375 on the Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells

作者：Chen, Si; Zheng, Yunfei; Zhang, Shan; Jia, Lingfei^*; Zhou, Yongsheng^*

来源：Stem Cell Reports, 2017, 8(3): 773-786.

DOI：10.1016/j.stemcr.2017.01.028

• HIPPO PATHWAY
• SIGNALING PATHWAY
• BONE-FORMATION
• YAP
• PROLIFERATION
• DEPTOR
• TISSUE
• TAZ
• CARCINOMA
• MICRORNAS

MicroRNAplays an important role in bone tissue engineering; however, its role and function in osteogenic differentiation warrant further investigation. In this study, we demonstrated that miR-375 was upregulated during the osteogenic differentiation of human adiposederived mesenchymal stem cells (hASCs). Overexpression of miR-375 significantly enhanced hASCs osteogenesis both in vitro and in vivo, while knockdown of miR-375 inhibited the osteogenic differentiation of hASCs. Mechanistically, microarray analysis revealed DEPTOR as a target of miR-375 in hASCs. Knockdown of DEPTOR accelerated the osteogenic differentiation of hASCs by inhibiting AKT signaling, which mimics miR-375 overexpression. Furthermore, we confirmed that miR-375 regulated osteogenesis by targeting YAP1, and that YAP1 reversely bound to miR-375 promoter to inhibit miR-375 expression. Taken together, our results suggested that miR-375 promoted the osteogenic differentiation of hASCs via the YAP1/DEPTOR/AKT regulatory network, indicating that miR-375-targeted therapy might be a valuable approach to promote bone regeneration.

• 出版日期2017-3-14
• 单位北京大学