Sun Yufeng, Liu Wei, Zhang Hao, Li Hongtao, Liu Jiakun, Zhang Fayao, Jiang Tao, Jiang Shan
1 Department of Orthopaedics, The Fifth Hospital of Harbin , Harbin, China .
2 Department of Orthopaedics, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine , Harbin, China .
J Interferon Cytokine Res. 2017 Oct;37(10):449-455. doi: 10.1089/jir.2017.0069.
Curcumin has shown protective potential on osteoarthritis. However, its effect on treatment of osteoarthritis remains elusive so far. This study aimed to determine whether curcumin could ameliorate osteoarthritis in vivo and the underline mechanisms. The mice subjected to destabilization of the medial meniscus (DMM) surgery were administered curcumin. Cartilage integrity was evaluated by immunohistological staining. Expression levels of inflammatory cytokines from mice arthrodial cartilage were detected. THP-1 cells were primed by lipopolysaccharide (LPS)/ATP to induce inflammation, followed by the addition of curcumin. The expression of proinflammatory cytokines was also detected. Moreover, the expression of pro-caspase-1, cleaved caspase-1, and NLRP3 inflammasome was examined. Administration of curcumin significantly reduced osteoarthritis disease progression in DMM model of osteoarthritis. Curcumin suppressed mRNA expression of proinflammatory mediators in arthrodial cartilage of mice subjected to surgery. In LPS- and ATP-induced THP-1 macrophage cells, curcumin significantly suppressed the expression of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) at both RNA and protein levels. Compared to vehicle-treated controls, curcumin also showed remarkably increased pro-caspase-1 and decreased cleaved caspase-1. This study provides the first evidence that curcumin exerts protection on osteoarthritis by inhibition to the release of inflammasome NLRP3, leading to the downregulation of inflammatory cytokines.
姜黄素已显示出对骨关节炎的保护潜力。然而，其对骨关节炎的治疗效果迄今仍不明确。本研究旨在确定姜黄素是否能在体内改善骨关节炎及其潜在机制。对接受内侧半月板不稳定（DMM）手术的小鼠给予姜黄素。通过免疫组织学染色评估软骨完整性。检测小鼠关节软骨中炎性细胞因子的表达水平。用脂多糖（LPS）/ATP预处理THP-1细胞以诱导炎症，随后添加姜黄素。还检测促炎细胞因子的表达。此外，检测前半胱天冬酶-1、裂解的半胱天冬酶-1和NLRP3炎性小体的表达。给予姜黄素可显著降低骨关节炎DMM模型中骨关节炎疾病的进展。姜黄素抑制了接受手术小鼠关节软骨中促炎介质的mRNA表达。在LPS和ATP诱导的THP-1巨噬细胞中，姜黄素在RNA和蛋白质水平上均显著抑制白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）的表达。与载体处理的对照组相比，姜黄素还显著增加了前半胱天冬酶-1的表达并降低了裂解的半胱天冬酶-1的表达。本研究提供了首个证据，即姜黄素通过抑制炎性小体NLRP3的释放来对骨关节炎发挥保护作用，从而导致炎性细胞因子的下调。
