miR-155 Regulates GSK-3 beta Expression and Affects Cartilage Matrix Degradation in the Pathogenesis of Osteoarthritis

摘要

Abnormal expression of GSK-3 beta is associated with the pathogenesis of osteoarthritis (OA). The miR-155 expression in cartilage tissue of OA patients was significantly elevated. A relationship between miR-155 and GSK-3 beta is predicted by the software. This study investigated whether miR155 regulates GSK-3 beta expression, affects Wnt/beta-catenin pathway activity in OA. The cartilage tissues of OA patients and normal cartilage tissues after traumatic amputation were collected. The OA rat model was established and divided into OA+ antagomir control group, OA+ miR-155 antagomir group followed by analysis of expression of miR-155, GSK-3 beta, beta-catenin and COL2A1 by qRT-PCR, Hyp content by ELISA, caspase-3 activity, and GSK-3 beta, beta-catenin, COL2A1 expression by western blot. Compared to control group, the expression of miR-155 and beta-catenin in cartilage tissue of OA patients was significantly elevated and GSK-3 beta level was reduced. There was a targeted regulation relationship between miR-155 and GSK-3 beta. OA group had significantly higher miR-155 and beta-catenin expression and lower GSK-3 beta and COL2A1 level in the cartilage than sham group. Compared with OA+ antagomir control group, miR-155 and beta-catenin expression and caspase-3 activity in OA+ miR-155 antagomir group were significantly decreased, with increased expression of GSK-3 beta and COL2A1 and reduced Hyp content. Increased miR-155 expression can decrease GSK-3 beta expression, enhance Wnt/beta-catenin pathway activity, promote the degradation and destruction of cartilage matrix and inhibit miR-155 expression, thus ameliorating the development and progress of OA.