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

被引:72
作者
Chen, Si [1 ]
Zheng, Yunfei [2 ]
Zhang, Shan [3 ]
Jia, Lingfei [3 ,4 ]
Zhou, Yongsheng [1 ,5 ]
机构
[1] Peking Univ, Sch & Hosp Stomatol, Dept Prosthodont, 22 Zhongguancun South Ave, Beijing 100081, Peoples R China
[2] Peking Univ, Sch & Hosp Stomatol, Dept Orthodont, 22 Zhongguancun South Ave, Beijing 100081, Peoples R China
[3] Peking Univ, Sch & Hosp Stomatol, Cent Lab, 22 Zhongguancun South Ave, Beijing 100081, Peoples R China
[4] Peking Univ, Sch & Hosp Stomatol, Dept Oral & Maxillofacial Surg, 22 Zhongguancun South Ave, Beijing 100081, Peoples R China
[5] Peking Univ, Sch & Hosp Stomatol, Beijing Key Lab Digital Stomatol, Natl Engn Lab Digital & Mat Technol Stomatol, 22 Zhongguancun South Ave, Beijing 100081, Peoples R China
基金
中国国家自然科学基金;
关键词
HIPPO PATHWAY; SIGNALING PATHWAY; BONE-FORMATION; YAP; PROLIFERATION; DEPTOR; TISSUE; TAZ; CARCINOMA; MICRORNAS;
D O I
10.1016/j.stemcr.2017.01.028
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:773 / 786
页数:14
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