Quercitrin alleviates cartilage extracellular matrix degradation and delays ACLT rat osteoarthritis development: an in vivo and in vitro study

Abstract Disruptions of extracellular matrix (ECM) degradation homeostasis play a significant role in the pathogenesis of osteoarthritis (OA). Matrix metalloproteinase 13 (MMP13) and collagen Ⅱ are important components of ECM. Earlier we found that quercitrin could significantly decrease MMP13 gene expression and increase collagen Ⅱ gene expression in IL-1β-induced rat chondrocytes and SW1353 cells. On this basis, we further explored the mechanism of quercitrin on OA. In vitro, quercitrin promoted cell proliferation and delayed ECM degradation by regulating MMP13 and collagen II gene and protein expressions. Moreover, quercitrin activated the Phosphatidylinositol 3-kinase p110α (p110α)/AKT/mTOR signaling pathway by targeting p110α. We also firstly showed that the gene expression level of p110α was remarkably decreased in cartilage of OA patients. To further investigate the effect of quercitrin in vivo, an anterior cruciate ligament transection rat model of OA was used. The results showed that intra-articular injection of quercitrin increased bone volume/tissue volume of tibial subchondral bone and cartilage thickness and reduced the Osteoarthritis Research Society International scores in OA rats. Meanwhile, Immunohistochemical results showed that quercitrin exerted anti-OA effect by delaying ECM degradation. These findings suggested that quercitrin may be a prospective disease-modifying OA drug for prevention and treatment of early stage OA.