4.6 Article

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

期刊

STEM CELL REPORTS
卷 8, 期 3, 页码 773-786

出版社

CELL PRESS
DOI: 10.1016/j.stemcr.2017.01.028

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资金

  1. National Natural Science Foundation of China [81371118, 81402235]
  2. Culturing Program for Leading Talents in Beijing Science and Technology Innovation [Lj201725]
  3. Ph.D. Programs Foundation of Ministry of Education of China [20130001110101]
  4. foundation of the Peking University School and Hospital of Stomatology [PKUSS20140104]

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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.

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