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

Abstract

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.

Gentiopicroside ameliorates the lipopolysaccharide-induced inflammatory response and hypertrophy in chondrocytes

“…Recombinant A disintegrin and metalloproteinase with thrombospondin (ADAMTS) is a protease that mediates the degradation of the ECM of chondrocytes, leading to the destruction of cartilage integrity and the degradation of aggrecan [ 42 ]. Even in the early stages of KOA, significant expression of ADAMTS5 was observed in articular cartilage [ 43 ]. Little et al showed that compared with wild-type mice, OA model mice with whole-gene MMP-13 knockout exhibited relatively reduced articular cartilage degradation, whereas MMP-13 overexpression aggravated the progression of OA [ 44 ].…”

Effects of Different Running Intensity on Serum Levels of IL-6 and TNF-alpha in Patients with Early Knee Osteoarthritis

“…Therefore, the knee joint is prone to joint damage due to joint mechanical damage during daily exercise and walking, and chronic joint injuries caused by over-work and trauma are the main influencing factors of knee degeneration and the main cause of KOA. 11,12 Clinically, the method for the treatment of KOA is comprehensively selected based on patients' conditions. For patients with mild conditions, conservative treatment with medicines is recommended, while for those with moderate and severe conditions, HTO surgery is preferred, which can effectively ameliorate the clinical symptoms of patients and improve their quality of life and prognosis.…”

Inflammatory Process on Knee Osteoarthritis in Cyclists

“…Thus, the knee joint is prone to damage due to mechanical stresses during the execution of high-intensity daily exercise. Therefore, chronic joint injuries caused by overwork and trauma are the main factors influencing knee degeneration and the major cause of OA in athletes [75]. Different studies indicate that after the onset of inflammation, blood levels of IL-1β, IL-6 and TNF-α increase [75][76][77][78][79].…”

“…Therefore, chronic joint injuries caused by overwork and trauma are the main factors influencing knee degeneration and the major cause of OA in athletes [75]. Different studies indicate that after the onset of inflammation, blood levels of IL-1β, IL-6 and TNF-α increase [75][76][77][78][79]. These increases are even more evident in patients diagnosed with arthritis caused by injury to knee articular cartilage [80].…”