Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, China.
Department of Orthopedics, The Second Hospital of Jilin University, Changchun, China.
J Cell Biochem. 2018 Sep;119(9):7419-7430. doi: 10.1002/jcb.27051. Epub 2018 May 28.
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-1β (IL-1β)-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-1β. 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-κB pathway were detected by Western blot. Ligustrazine significantly suppressed inflammatory reaction in joint effusion of OA patients. Moreover, ligustrazine attenuated IL-1β-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-1β-induced chondrocytes. Besides, ligustrazine increased SOX9 expression, and SOX9 silencing reversed the effect of ligustrazine on matrx degradation in IL-1β-injured chondrocytes. Furthermore, ligustrazine blocked NF-κB pathway in IL-1β-induced chondrocytes, and PTDC (NF-κB inhibitor) enhanced the effect of ligustrazine on viability, apoptosis, SOX9 expression, and ROS production in IL-1β-induced chondrocytes. These results indicated that ligustrazine protected chondrocytes against IL-1β-induced injury possibly by regulation of SOX9 and inactivation of NF-κB signaling pathway. It could act as a therapeutic agent for the treatment of OA.
川芎嗪从川芎中提取，在传统中药中以其血管扩张特性而闻名。本研究旨在确定川芎嗪对骨关节炎（OA）中白细胞介素-1β（IL-1β）诱导损伤的作用及其潜在机制。从 OA 患者的关节软骨和关节液中获得人关节软骨和关节液，并分离软骨细胞并用 IL-1β处理。通过 ELISA 分析不同的炎症细胞因子。通过 MTT、流式细胞术和 Western blot 检测细胞活力、细胞凋亡和与细胞凋亡相关的因素。然后，测量 COL2A1 和 ACAN 的表达以及 sGAG 和 MMP-13 的浓度。分析 SOD 和 MDA 水平以及 ROS 产生。此外，通过 Western blot 检测 SOX9 和 NF-κB 通路的蛋白水平。川芎嗪显著抑制 OA 患者关节液中的炎症反应。此外，川芎嗪减轻了 IL-1β诱导的软骨细胞损伤和基质降解。川芎嗪通过增加 SOD 水平、降低 MDA 水平和抑制 IL-1β诱导的软骨细胞中的 ROS 产生来促进氧化应激反应。此外，川芎嗪增加了 SOX9 的表达，而 SOX9 沉默逆转了川芎嗪对 IL-1β损伤软骨细胞中基质降解的作用。此外，川芎嗪阻断了 IL-1β诱导的软骨细胞中的 NF-κB 途径，而 PTDC（NF-κB 抑制剂）增强了川芎嗪对 IL-1β诱导的软骨细胞中活力、凋亡、SOX9 表达和 ROS 产生的作用。这些结果表明，川芎嗪通过调节 SOX9 和失活 NF-κB 信号通路来保护软骨细胞免受 IL-1β诱导的损伤，可作为治疗 OA 的治疗剂。
