miR‐148a regulates osteoclastogenesis by targeting V‐maf musculoaponeurotic fibrosarcoma oncogene homolog B

• Published in: Journal of bone and mineral research Vol. 28; no. 5; pp. 1180 - 1190
• Main Authors: Cheng, Peng, Chen, Chao, He, Hong‐Bo, Hu, Rong, Zhou, Hou‐De, Xie, Hui, Zhu, Wu, Dai, Ru‐Chun, Wu, Xian‐Ping, Liao, Er‐Yuan, Luo, Xiang‐Hang
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2013; Wiley Subscription Services, Inc
• Subjects: Bone and Bones - metabolism; Case-Control Studies; Cell Differentiation; Humans; Lupus Erythematosus, Systemic - metabolism; Lupus Erythematosus, Systemic - pathology; MAFB; MafB Transcription Factor - genetics; MICRORNA; MicroRNAs - physiology; Monocytes - immunology; OSTEOCLASTOGENESIS; Osteoclasts - cytology; OSTEOPOROSIS; PBMCS; Up-Regulation
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1002/jbmr.1845

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. © 2013 American Society for Bone and Mineral Research.