title: A novel microRNA regulates osteoclast differentiation via targeting protein inhibitor of activated STAT3 (PIAS3).
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.
authors.affiliation: Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, 139# Middle Renmin Road, Changsha, Hunan 410011, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Hunan Province Geriatric Hospital, 89# Guhan Road, Changsha, Hunan 410001, PR China.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Qin
authors.affiliation: Department of Endocrinology, Hunan Province Geriatric Hospital, 89# Guhan Road, Changsha, Hunan 410001, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liao
authors.affiliation: Department of Endocrinology, Changsha Central Hospital, 161# Shaoshan Road, Changsha, Hunan 410004, PR China.
authors.forename: Hui-Ge
authors.initials: HG
authors.lastname: Shao
authors.affiliation: Department of Endocrinology, Xiangya Hospital of Central South University, 87# Xiangya Road, Changsha, Hunan 410008, PR China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Guo
authors.affiliation: Department of Endocrinology, Changsha Central Hospital, 161# Shaoshan Road, Changsha, Hunan 410004, PR China. Electronic address: genqingxie@gmail.com.
authors.forename: Gen-Qing
authors.initials: GQ
authors.lastname: Xie
authors.affiliation: Department of Endocrinology, Hunan Province Geriatric Hospital, 89# Guhan Road, Changsha, Hunan 410001, PR China; Department of Endocrinology, Xiangya Hospital of Central South University, 87# Xiangya Road, Changsha, Hunan 410008, PR China. Electronic address: run850218@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Xiangya Hospital of Central South University, 87# Xiangya Road, Changsha, Hunan 410008, PR China. Electronic address: jiangtiejian@gmail.com.
authors.forename: Tie-Jian
authors.initials: TJ
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology
chemical_list: D035683:MicroRNAs; C109279:Pias3 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D053245:RANK Ligand; D016173:Macrophage Colony-Stimulating Factor
keywords: Bone; Differentiation; MicroRNA; Osteoclast; PIAS3