MicroRNA-186 ameliorates Knee osteoarthritis via regulation of P2X7-mediated Cathepsin-K/Runx2/ADAMTS5 signalling axis in articular chondrocytes

摘要

Knee osteoarthritis (KOA) is a chronic joint disorder involving the articular cartilage and tissues around the synovial joint. The key objective of this study was to determine the effect of miR-186-5p administration on the expression of pathogenic signalling in the chondrocytes using a surgical destabilization of the medial meniscus (DMM) model of KOA, and to testify the mechanism of P2X7-mediated regulation of RUNX2/ADAMTS5 axis by miR-186 in the KOA rats. After eight weeks of intra-articular injection of the miR-186-5p and negative control lentivirus samples, the knee cartilage tissues were subjected to histopathological analysis Safranin-O/Fast green staining. Further, the articular chondrocytes were separated and analysed for various proteins including P2X7, cathepsin-K, RUNX2 and ADAMTS5 using Western blotting method. We observed that the protein expressions of P2X7, cathepsin-K/RUNX2/ADAMTS5, and also MMP-13 were upmodulated in the KOA rats, while intra-articular miR-186-5p lentivirus administration prevented these aberrations. Hence, the study concludes that miR-186 orchestrates P2X7 expression and the P2X7-mediated cathepsin-K/RUNX2/ADAMTS5 axis and regulates the pathogenesis of KOA. In light of this evidence, we propose that molecular therapeutic interventions targeting miR-186 activation might attenuate osteoarthritic cartilage degeneration.