Ligustrazine protects chondrocyte against IL-1 induced injury by regulation of SOX9/NF-B signaling pathway

摘要

Ligustrazine is extracted from rhizoma ligustici wallichii, is known for its vasodilatory properties in the traditional Chinese herbal medicine. The study aimed to determine the effect and the underlying mechanism of ligustrazine on interleukin-1 (IL-1)-induced injury in osteoarthritis (OA). Human articular cartilages and joint effusion were obtained from patients with OA, and the chondrocytes were isolated and treated with IL-1. The different inflammatory cytokines were analyzed by ELISA. Cell viability, apoptosis, and apoptosis-related factors were examined by MTT, flow cytometry, and Western blot. Then, the expressions of COL2A1 and ACAN, and the concentrations of sGAG and MMP-13 were measured. The level of SOD and MDA and ROS production were then analyzed. Furthermore, the protein levels of SOX9 and NF-B pathway were detected by Western blot. Ligustrazine significantly suppressed inflammatory reaction in joint effusion of OA patients. Moreover, ligustrazine attenuated IL-1-induced chondrocytes injury and matrx degradation in chondrocytes. Ligustrazine promoted oxidative stress response by increasing SOD level, decreasing MDA level, and inhibiting ROS production in IL-1-induced chondrocytes. Besides, ligustrazine increased SOX9 expression, and SOX9 silencing reversed the effect of ligustrazine on matrx degradation in IL-1-injured chondrocytes. Furthermore, ligustrazine blocked NF-B pathway in IL-1-induced chondrocytes, and PTDC (NF-B inhibitor) enhanced the effect of ligustrazine on viability, apoptosis, SOX9 expression, and ROS production in IL-1-induced chondrocytes. These results indicated that ligustrazine protected chondrocytes against IL-1-induced injury possibly by regulation of SOX9 and inactivation of NF-B signaling pathway. It could act as a therapeutic agent for the treatment of OA.