Curcumin ameliorates IL-1β-induced apoptosis by activating autophagy and inhibiting the NF-κB signaling pathway in rat primary articular chondrocytes
Curcumin ameliorates IL-1β-induced apoptosis by activating autophagy and inhibiting the NF-κB signaling pathway in rat primary articular chondrocytes
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DOI：
10.1002/cbin.11541
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发表时间：
2021-01-25
影响因子：
3.9
通讯作者：
Lu, Chao
中科院分区：
文献类型：
--
作者：
Chen, Tianyi;Zhou, Renpeng;Lu, Chao
关节软骨损伤和软骨细胞凋亡是类风湿关节炎和骨关节炎的共同特征。最近，姜黄素被报道对关节软骨疾病退行性变有保护作用。然而，姜黄素对关节软骨细胞损伤的影响及其机制尚不清楚。本研究旨在探讨姜黄素在体外对白细胞介素-1 β (IL-1 β)诱导的软骨细胞凋亡的保护机制。结果显示，IL-1 β降低了原代关节软骨细胞的细胞活力并诱导细胞凋亡。姜黄素预处理可减少IL-1 β诱导的关节软骨细胞凋亡。此外，姜黄素治疗增加了关节软骨细胞的自噬，并防止IL-1 β诱导的细胞凋亡。当细胞被自噬抑制剂3-甲基腺嘌呤处理或转染Beclin-1小干扰RNA时，姜黄素介导的对IL-1 β诱导的凋亡的保护作用被消除。此外，IL-1 β刺激显著增加了核因子(NF)- κ B p65和糖原合成酶激酶-3 β的磷酸化水平，降低了关节软骨细胞中β -连环蛋白的磷酸化水平，姜黄素处理部分逆转了磷酸化水平的变化。双荧光素酶和电泳迁移转移实验表明，IL-1 β增加了软骨细胞中NF-kappa B p65启动子的活性，姜黄素也能逆转这种情况。NF-kappa B抑制剂吡咯烷二硫代氨基甲酸酯预处理增强了姜黄素对软骨细胞凋亡的保护作用，但Wnt/ β -连环蛋白抑制剂XAV-939没有表现出这种作用。分子对接和动态模拟研究结果表明，姜黄素可以与RelA （p65）蛋白结合。提示姜黄素可能通过激活自噬和抑制nf - κ B信号通路抑制IL-1 β诱导的软骨细胞凋亡。
Articular cartilage damage and chondrocyte apoptosis are common features of rheumatoid arthritis and osteoarthritis. Recently, curcumin has been reported to exhibit protective effects on degeneration in articular cartilage diseases. However, the effects and mechanisms of curcumin on articular chondrocyte injury remain to be elucidated. The aim of the present study is to investigate the chondroprotective mechanisms of curcumin on interleukin-1 beta (IL-1 beta)-induced chondrocyte apoptosis in vitro. The results revealed that IL-1 beta decreased cell viability and induced apoptosis in primary articular chondrocytes. Curcumin pretreatment reduced IL-1 beta-induced articular chondrocyte apoptosis. In addition, treatment with curcumin increased autophagy in articular chondrocytes and protected against IL-1 beta-induced apoptosis. The curcumin-mediated protection against IL-1 beta induced apoptosis was abolished when cells were treated with the autophagy inhibitor 3-methyladenine or transfected with Beclin-1 small interfering RNA. Furthermore, IL-1 beta stimulation significantly increased the phosphorylation levels of nuclear factor (NF)-kappa B p65 and glycogen synthase kinase-3 beta, and decreased the phosphorylation levels of beta-catenin in articular chondrocytes, and these alterations to the phosphorylation levels were partly reversed by treatment with curcumin. Dual-luciferase and electrophoretic mobility shift assays demonstrated that IL-1 beta increased NF-kappa B p65 promoter activity in chondrocytes, and this was also reversed by curcumin. Pretreatment with the NF-kappa B inhibitor pyrrolidine dithiocarbamate enhanced the protective effects of curcumin on chondrocyte apoptosis, but Wnt/beta-catenin inhibitor, XAV-939, did not exhibit this effect. Molecular docking and dynamic simulation studies results showed that curcumin could bound to RelA (p65) protein. These results indicate that curcumin may suppress IL-1 beta-induced chondrocyte apoptosis through activating autophagy and restraining NF-kappa B signaling pathway.