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miR-148a regulates osteoclastogenesis by targeting V-maf musculoaponeurotic fibrosarcoma oncogene homolog B.
- Source :
- Journal of Bone & Mineral Research; May2013, Vol. 28 Issue 5, p1180-1190, 11p
- Publication Year :
- 2013
-
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. © 2013 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08840431
- Volume :
- 28
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Journal of Bone & Mineral Research
- Publication Type :
- Academic Journal
- Accession number :
- 87016351
- Full Text :
- https://doi.org/10.1002/jbmr.1845