MicroRNA-377–3p alleviates IL-1β-caused chondrocyte apoptosis and cartilage degradation in osteoarthritis in part by downregulating ITGA6

• Published in: Biochemical and biophysical research communications 2020-02, Vol.523 (1), p.46-53
• Main Authors: Tu, Yihui, Ma, Tong, Wen, Tao, Yang, Tao, Xue, Long, Cai, Minwei, Wang, Fangxin, Guan, Mengying, Xue, Huaming
• Format: Article
• Language: English
• Subjects: Chondrocyte; Extracellular-matrix degradation; Inflammatory response; ITGA6; miR-377–3p; Osteoarthritis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.11.186

Increasing evidence indicates that altered expression of microRNAs (miRNAs) is associated with osteoarthritis (OA) progression. In our study, we demonstrated that miR-377–3p is underexpressed in OA-affected cartilage and IL-1β–treated chondrocytes. Overexpression of miR-377–3p enhanced chondrocyte proliferation and restrained apoptosis and signs of cartilage matrix degradation and of an inflammatory response. Furthermore, ITGA6 was identified as a target gene of miR-377–3p. The latter was found to directly bind to the 3′ untranslated region (3′UTR) of ITGA6 mRNA and downregulate ITGA6. In addition, ITGA6 expression was high in OA-affected tissues and negatively correlated with miR-77–3p expression. Overexpression of ITGA6 reversed the effects of miR-377–3p on IL-1β–caused chondrocyte apoptosis, cartilage matrix degradation, and the inflammatory response. Moreover, bioinformatic analysis and a luciferase assay indicated that miR-377–3p expression is regulated by long noncoding RNA NEAT1, which binds to miR-377–3p and inactivates it. We showed that NEAT1 was highly expressed in OA-affected cartilage, negatively correlated with miR-377–3p levels, and positively correlated with ITGA6 levels. These findings provide information for the development of future treatments of OA, suggesting that miR-377–3p may be a therapeutic target in OA. •MiR-377 expression is low in OA-affected cartilage and IL-1β–treated chondrocytes.•Effects of miR-377–3p on proliferation and apoptosis of IL-1β–treated chondrocytes.•Effects of miR-377–3p on signs of cartilage matrix degradation and of an inflammatory response in IL-1β–treated chondrocytes.•ITGA6 overexpression reverses the negative effect of miR-377–3p on IL-1β–induced chondrocyte apoptosis and signs of the inflammatory response.•NEAT1 promotes ITGA6 expression by sponging miR-377–3p in chondrocytes.