title: microRNA-23a inhibits osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting LRP5.
abstract: Emerging evidence indicates that microRNAs (miRNA, or miR) play vital roles in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Elucidation of the molecular mechanisms that govern BMSCs osteogenic differentiation is of paramount importance for improving the treatment of bone-related diseases. In our current study, we investigated the role of miR-23a in BMSCs osteogenesis. Our results revealed that miR-23a was significantly downregulated during osteogenic differentiation. Overexpression of miR-23a inhibited osteogenic differentiation of hBMSCs in vitro, whereas downregulation of miR-23a enhanced the process. Target prediction analysis and dual luciferase reporter assays confirmed that low-density lipoprotein (LDL)-receptor-related protein 5 (LRP5) was a direct target of miR-23a. Furthermore, knockdown of LRP5 inhibited osteogenic differentiation of hBMSCs, similar to the effect observed in upregulation miR-23a. Our data indicate that miR-23a plays an inhibitory role in osteogenic differentiation of hBMSCs, which may act by targeting LRP5.
authors.affiliation: Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Basic Medical Sciences and School of Basic Medicine, Beijing 100005, China.
authors.forename: Hongling
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Yingzhen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Basic Medical Sciences and School of Basic Medicine, Beijing 100005, China.
authors.forename: Tangping
authors.initials: T
authors.lastname: Li
authors.affiliation: Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Basic Medical Sciences and School of Basic Medicine, Beijing 100005, China.
authors.forename: Junfen
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xiao
authors.affiliation: Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Basic Medical Sciences and School of Basic Medicine, Beijing 100005, China.
authors.forename: Robert Chunhua
authors.initials: RC
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China. Electronic address: xshweng@medmail.com.cn.
authors.forename: Xisheng
authors.initials: X
authors.lastname: Weng
mesh_terms: D000328:Adult; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000172:deficiency / Q000235:genetics*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics*; D010641:Phenotype; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C552430:MIRN23a microRNA, human; D035683:MicroRNAs
keywords: Human bone marrow-derived mesenchymal stem cells; LRP5; Osteogenic differentiation; microRNA-23a