title: MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis.
abstract: MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. In the present study, we found that miR-125a was dramatically down-regulated during macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclastogenesis of circulating CD14+ peripheral blood mononuclear cells (PBMCs). Overexpression of miR-125a in CD14+ PBMCs inhibited osteoclastogenesis, while inhibition of miR-125a promoted osteoclastogenesis. TNF receptor-associated factor 6 (TRAF6), a transduction factor for RANKL/RANK/NFATc1 signal, was confirmed to be a target of miR-125a. EMSA and ChIP assays confirmed that NFATc1 bound to the promoter of the miR-125a. Overexpression of NFATc1 inhibited miR-125a transcription, and block of NFATc1 expression attenuated RANKL-regulated miR-125a transcription. Here, we reported that miR-125a played a biological function in osteoclastogenesis through a novel TRAF6/ NFATc1/miR-125a regulatory feedback loop. It suggests that regulation of miR-125a expression may be a potential strategy for ameliorating metabolic disease.
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, Xiangya Hospital of Central South University, 87# Xiangya Road, Changsha, Hunan 410008, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Liao
authors.affiliation: Department of Endocrinology, Hunan Province Geriatric Hospital, Changsha, Hunan 410001, PR China.
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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
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: D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D018390:Gene Targeting; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D053245:RANK Ligand / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D048029:TNF Receptor-Associated Factor 6 / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D018950:Lipopolysaccharide Receptors; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D053245:RANK Ligand; D034741:RNA, Small Interfering; D048029:TNF Receptor-Associated Factor 6; D016173:Macrophage Colony-Stimulating Factor
keywords: MicroRNA; Osteoclastogenesis; TRAF6