title: miR-148a regulates osteoclastogenesis by targeting V-maf musculoaponeurotic fibrosarcoma oncogene homolog B.
abstract: MicroRNAs (miRNAs) play crucial roles in bone metabolism. In the present study, we found that miR-148a is dramatically upregulated during osteoclastic differentiation of circulating CD14+ peripheral blood mononuclear cells (PBMCs) induced by macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). Overexpression of miR-148a in CD14+ PBMCs promoted osteoclastogenesis, whereas inhibition of miR-148a attenuated osteoclastogenesis. V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) is a transcription factor negatively regulating RANKL-induced osteoclastogenesis. miR-148a directly targeted MAFB mRNA by binding to the 3' untranslated region (3'UTR) and repressed MAFB protein expression. In vivo, our study showed that silencing of miR-148a using a specific antagomir-inhibited bone resorption and increased bone mass in mice receiving ovariectomy (OVX) and in sham-operated control mice. Furthermore, our results showed that miR-148a levels significantly increased in CD14+ PBMCs from lupus patients and resulted in enhanced osteoclastogenesis, which contributed to the lower bone mineral density (BMD) in lupus patients compared with normal controls. Thus, our study provides a new insight into the roles of miRNAs in osteoclastogenesis, and contributes to a new therapeutic pathway for osteoporosis.
authors.affiliation: Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: He
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Hou-De
authors.initials: HD
authors.lastname: Zhou
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Wu
authors.initials: W
authors.lastname: Zhu
authors.forename: Ru-Chun
authors.initials: RC
authors.lastname: Dai
authors.forename: Xian-Ping
authors.initials: XP
authors.lastname: Wu
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Liao
authors.forename: Xiang-Hang
authors.initials: XH
authors.lastname: Luo
mesh_terms: D001842:Bone and Bones / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology; D051258:MafB Transcription Factor / Q000235:genetics*; D035683:MicroRNAs / Q000502:physiology*; D009000:Monocytes / Q000276:immunology; D010010:Osteoclasts / Q000166:cytology*; D015854:Up-Regulation
chemical_list: C490407:MAFB protein, human; C550570:MIRN148 microRNA, human; D051258:MafB Transcription Factor; D035683:MicroRNAs