1. A novel microRNA regulates osteoclast differentiation via targeting protein inhibitor of activated STAT3 (PIAS3).
- Author
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Liu T, Qin AP, Liao B, Shao HG, Guo LJ, Xie GQ, Yang L, and Jiang TJ
- Subjects
- Animals, Cell Differentiation genetics, Cell Line, Cells, Cultured, Macrophage Colony-Stimulating Factor pharmacology, Mice, MicroRNAs genetics, Protein Inhibitors of Activated STAT genetics, RANK Ligand pharmacology, Cell Differentiation physiology, MicroRNAs physiology, Osteoclasts cytology, Osteoclasts metabolism, Protein Inhibitors of Activated STAT metabolism
- Abstract
MicroRNAs (miRNAs) involve in the regulation of a wide range of physiological processes. Recent studies suggested that miRNAs might play a role in osteoclast differentiation. Here, we identify a new miRNA (miR-9718) in primary mouse osteoclasts that promotes osteoclast differentiation by repressing protein inhibitor of activated STAT3 (PIAS3) at the post-transcriptional level. MiR-9718 was found to be transcribed during osteoclastogenesis, which was induced by macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). Overexpression of miR-9718 in RAW 264.7 cells promoted M-CSF and RANKL-induced osteoclastogenesis, whereas inhibition of miR-9718 attenuated it. PIAS3 was predicted to be a target of miR-9718. Luciferase reporter gene validated the prediction. Transfection of pre-miR-9718 in RAW 264.7 cells induced by both M-CSF and RANKL inhibited expression of PIAS3 protein, while the mRNA levels of PIAS3 were not attenuated. In vivo, our study showed that silencing of miR-9718 using a specific antagomir inhibited bone resorption and increased bone mass in mice receiving ovariectomy (OVX) and in sham-operated control mice. Thus, our study showed that miR-9718 played an important role in osteoclast differentiation via targeting PIAS3 both in vitro and in vivo., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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