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Publication : A novel microRNA regulates osteoclast differentiation via targeting protein inhibitor of activated STAT3 (PIAS3).

First Author  Liu T Year  2014
Journal  Bone Volume  67
Pages  156-65 PubMed ID  25019593
Mgi Jnum  J:215623 Mgi Id  MGI:5605921
Doi  10.1016/j.bone.2014.07.004 Citation  Liu T, et al. (2014) A novel microRNA regulates osteoclast differentiation via targeting protein inhibitor of activated STAT3 (PIAS3). Bone 67:156-65
abstractText  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-kappaB 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.
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