PP2 alleviates the progression of osteoarthritis by inhibiting Wnt/β-catenin and activating TGF- β/Smad signaling

Abstract

Objective Explore the effect and mechanism of Src inhibitor PP2 on knee osteoarthritis. Methods The protein expressions of Src, p-Src (y418) and p-FAK in normal and OA human chondrocytes were detected by immunofluorescence (IF). Chondrocytes from the femur and tibial plateau of 3-day-old mice were extracted and inoculated into 6-well plates. The chondrocytes were co-cultured with IL-1β and different doses of PP2, and then the degeneration of chondrocytes was observed. The OA model was induced by destabilizing medial meniscectomy in the right knee of mice; two weeks after the operation, different doses of PP2 were injected intraperitoneally. The medicine was given 3 times a week for 6 weeks, and then we took the knee cartilage of each group, and the degree of degeneration was observed. Results The levels of Src, p-Src (y418) and p-FAK in knee cartilage tissue of patients with OA were abnormally increased. After chondrocytes were co-treated with IL-1β and different doses of PP2, the results showed that PP2 could reduce the abnormal increase of β-catenin, p-β-catenin and other proteins created by IL-1β and reverse the decrease of p-Smad3, Aggrecan and collagen Ⅱ proteins. Meanwhile, intraperitoneal injection of PP2 in vivo significantly reduced the degeneration of articular cartilage. Conclusion Our data show that PP2 can inhibit Wnt/β-catenin and activate TGF-β/Smad signaling, thus protecting the cartilage of OA mice.