title: Promotion Effects of miR-375 on the Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells.
abstract: MicroRNA plays 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 adipose-derived 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.
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China; Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China. Electronic address: jialingfei1984@sina.com.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China; National Engineering Lab for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China. Electronic address: kqzhouysh@hsc.pku.edu.cn.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C556139:DEPTOR protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: DEPTOR; YAP1; bone regeneration; hASCs; mesenchymal stem cells; miR-375; microRNA; osteogenic differentiation