MicroRNA-142-3p Inhibits Chondrocyte Apoptosis and Inflammation in Osteoarthritis by Targeting HMGB1

• Published in: Inflammation 2016-10, Vol.39 (5), p.1718-1728
• Main Authors: Wang, Xiuqin, Guo, Yanqing, Wang, Chunyan, Yu, Hong, Yu, Xiuxiang, Yu, Hongbo
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Chondrocytes - pathology; Drug Delivery Systems; Gene Transfer Techniques; HMGB1 Protein - drug effects; Immunology; Inflammation - prevention & control; Inflammation - therapy; Internal Medicine; Mice; MicroRNAs - administration & dosage; MicroRNAs - genetics; MicroRNAs - pharmacology; MicroRNAs - physiology; NF-kappa B - metabolism; Original Article; Osteoarthritis - pathology; Osteoarthritis - therapy; Pathology; Pharmacology/Toxicology; Rheumatology; Signal Transduction
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-016-0406-3

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.