Rapamycin attenuates articular cartilage degeneration by inhibiting β-catenin in a murine model of osteoarthritis

Abstract

ABSTRACTPurpose: To investigate whether systemic injection of rapamycin attenuates articular cartilage degeneration by inhibiting β-catenin in a murine model of osteoarthritis (OA).Materials and methods: Ten-week-old male C57BL/6j wild-type (WT) mice and SOST-knockout (SOST−/−) mice were randomized to a sham group, a vehicle-treated group, and a rapamycin-treated group. Mice in the vehicle-treated group underwent destabilizing of the medial meniscus (DMM) in the right knee, and were then treated with vehicle. Mice in the rapamycin treatment group underwent DMM and were treated with rapamycin. Safranin O-Fast green staining and Osteoarthritis Research Society International (OARSI) modified Mankin score were used to evaluate the histopathological features of the articular cartilage in the knee. The expression of light chain 3 (LC3) was evaluated by immunofluorescence, whereas the expression of ATG5, matrix metallopeptidase 13 (MMP-13), vascular endothelial growth factor (VEGF), sclerostin, and β-catenin were evaluated by immunohistochemistry. TUNEL staining was used to determine apoptosis of chondrocytes.Results: In vehicle-treated mice when compared with mice in the sham group, the OARSI scores, expression of MMP-13, VEGF, sclerostin, β-catenin, and chondrocyte apoptosis were significantly increased, whereas the expression of LC3 and ATG5 were significantly decreased. A systemic injection of rapamycin activated chondrocyte autophagy, which increased the expression of LC3 and ATG-5, and reduced OARSI scores, the expression of β-catenin, MMP-13, and VEGF, and chondrocyte apoptosis in rapamycin treated mice when compared with vehicle-treated mice.Conclusions: Systemic injection of rapamycin attenuated articular cartilage degeneration by inhibiting β-catenin in a murine model of OA.