Attenuation of cartilage pathogenesis in osteoarthritis by blocking the phosphorylation of tyrosine kinase Fyn to beta-catenin, AZD0530

Objective: To observe the effect of AZD0530 on the progression of knee OA after blocking beta-catenin phosphorylation and then dormancy of the Wnt/beta pathway by tyrosine kinase Fyn. Methods: The levels of Fyn, beta-catenin, p-beta-catenin (Tyr142), the chondrocyte positive marker Aggrecan, and the chondrocyte negative marker MMP13 were observed in human knee tibial plateau chondrocytes in vivo and in vitro. Different doses of AZD0530 were used to treat chondrocytes of the human OA tibial plateau chondrocytes in vitro, and the degree of chondrocyte degeneration was observed. Different doses of AZD0530 were intra-articularly injected into OA rats to observe the degree of tibial plateau cartilage degeneration. Results: When OA occurred in human knee, the levels of tyrosine kinase Fyn, beta-catenin and p-beta-catenin (Tyr142) in chondrocytes increased significantly.The level of Aggrecan decreased and MMP13 increased in chondrocytes. The levels of beta-catenin, p-beta-catenin (Tyr142) and MMP13 in chondrocytes decreased, while the level of Aggrecan increased after AZD0530 was used to intervene chondrocytes in vitro, which was positively correlated with the dose of AZD0530. Intra-articular injection of AZD0530 obviously attenuated the degeneration of articular cartilage, which was positively correlated with the dose of AZD0530. Conclusion: The level of Fyn in chondrocytes of human knee tibial plateau increased significantly when OA occurred. AZD0530 can inhibit tyrosine kinase Fyn from beta-catenin phosphorylation, a key Wnt/beta pathway protein, and then inhibit Wnt/beta pathway levels in chondrocytes. This finding also suggests that disruption of the Wnt/beta pathway with AZD0530 provides chondral protection in rat posttraumatic OA.