title: MicroRNA-142-3p Inhibits Chondrocyte Apoptosis and Inflammation in Osteoarthritis by Targeting HMGB1.
abstract: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation and joint inflammation in which microRNAs are significantly involved. Previous studies have reported that miR-142-3p is a novel mediator of inflammatory signaling pathways, but whether miR-142-3p regulates OA remains unknown. In this study, we aimed to investigate the potential role of miR-142-3p in OA and the underlying molecular mechanism. We showed that miR-142-3p was significantly reduced in the articular cartilage tissues from experimental OA mice. The expression of miR-142-3p was also decreased in chondrocytes treated with lipopolysaccharide (LPS) in vitro. Moreover, the overexpression of miR-142-3p significantly inhibited cell apoptosis, nuclear factor (NF)-kB, and the production of proinflammatory cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α induced by LPS. Interestingly, bioinformatics analysis demonstrated that high mobility group box 1 (HMGB1), an important inflammatory mediator of OA, was predicted as a target of miR-142-3p, which was validated by dual-luciferase reporter assay. The high expression of HMGB1 in chondrocytes induced by LPS was significantly inhibited by miR-142-3p overexpression. Furthermore, the restoration of HMGB1 markedly abrogated the effect of miR-142-3p. In OA mice, the overexpression of miR-142-3p by lentivirus-mediated gene transfer significantly inhibited HMGB1 expression, NF-kB signaling, and proinflammatory cytokines. Moreover, the overexpression of miR-142-3p significantly alleviated OA progression in OA mice in vivo. Taken together, our study suggests that miR-142-3p inhibits chondrocyte apoptosis and inflammation in OA by inhibiting the HMGB1-mediated NF-kB signaling pathway. The overexpression of miR-142-3p impedes the OA progression in mice in vivo indicating that miR-142-3p is a potential molecular target for OA treatment.
authors.affiliation: Record Room, Weihai Municipal Hospital, Weihai, 264200, China.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Traumatology and Arthrosis, Weihai Municipal Hospital, No. 70 Heping Road, Weihai, 264200, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Operating Room, Weihai Municipal Hospital, Weihai, 264200, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Traumatology and Arthrosis, Weihai Municipal Hospital, No. 70 Heping Road, Weihai, 264200, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Traumatology and Arthrosis, Weihai Municipal Hospital, No. 70 Heping Road, Weihai, 264200, China.
authors.forename: Xiuxiang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Traumatology and Arthrosis, Weihai Municipal Hospital, No. 70 Heping Road, Weihai, 264200, China. yuhongbo_hb@sina.com.
authors.forename: Hongbo
authors.identifier: http://orcid.org/0000-0001-5372-1299
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019902:Chondrocytes / Q000473:pathology*; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D024243:HMGB1 Protein / Q000187:drug effects*; D007249:Inflammation / Q000517:prevention & control* / Q000628:therapy; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D010003:Osteoarthritis / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction
chemical_list: D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse; D016328:NF-kappa B
keywords: chondrocyte apoptosis; high mobility group box 1; inflammation; miR-142-3p; osteoarthritis