title: MiR-34a Promotes Osteogenic Differentiation of Human Adipose-Derived Stem Cells via the RBP2/NOTCH1/CYCLIN D1 Coregulatory Network.
abstract: MiR-34a was demonstrated to be upregulated during the osteogenic differentiation of human adipose-derived stem cells (hASCs). Overexpression of miR-34a significantly increased alkaline phosphatase activity, mineralization capacity, and the expression of osteogenesis-associated genes in hASCs in vitro. Enhanced heterotopic bone formation in vivo was also observed upon overexpression of miR-34a in hASCs. Mechanistic investigations revealed that miR-34a inhibited the expression of retinoblastoma binding protein 2 (RBP2) and reduced the luciferase activity of reporter gene construct comprising putative miR-34a binding sites in the 3' UTR of RBP2. Moreover, miR-34a downregulated the expression of NOTCH1 and CYCLIN D1 and upregulated the expression of RUNX2 by targeting RBP2, NOTCH1, and CYCLIN D1. Taken together, our results suggested that miR-34a promotes the osteogenic differentiation of hASCs via the RBP2/NOTCH1/CYCLIN D1 coregulatory network, indicating that miR-34a-targeted therapy could be a valuable approach to promote bone regeneration.
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, 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, Beijing 100081, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China; Central Laboratory, Peking University School and Hospital of Stomatology, 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, Beijing 100081, China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 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, Beijing 100081, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, 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, Beijing 100081, China.
authors.forename: Chanyuan
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, 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, Beijing 100081, China.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, 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, Beijing 100081, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, 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, Beijing 100081, China. Electronic address: kqzhouysh@hsc.pku.edu.cn.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; D050659:Core Binding Factor Alpha 1 Subunit; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C518459:RBP2 protein, human; D051880:Receptors, Notch; D054840:Retinol-Binding Proteins, Cellular; D019938:Cyclin D1