Department of Orthopaedic Surgery, Nanjing Medical University Affiliated Wuxi Second Hospital, 68 Zhongshan Road, 214001, Wuxi, China.
Inflammopharmacology. 2019 Feb;27(1):109-119. doi: 10.1007/s10787-018-0509-6. Epub 2018 Jul 5.
Triptolide has been widely reported to exhibit potential therapeutic value in multiple inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis. Although its safety and efficacy as an anti-inflammatory agent have been verified by many studies, the effect of triptolide on osteoarthritis (OA) was not clearly understood. In this study, we found that triptolide prevented OA development in a surgical destabilization of the medial meniscus (DMM) mouse model. In addition, triptolide inhibited both DMM-induced and LPS-induced expression of pro-inflammatory cytokines in the human monocytic cell line THP-1. Further mechanistic studies showed that the reduction of pro-inflammatory cytokines by triptolide was mediated by the upregulation of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) and downregulation of caspase-1. Finally, we identified that hsa-miR-20b, a microRNA targeting the NLRP3 gene, was downregulated by triptolide. This study provides a novel insight into the effect on triptolide in preventing OA pathogenesis.
雷公藤红素在多种炎症性疾病中具有潜在的治疗价值，如类风湿性关节炎、系统性红斑狼疮和银屑病等，这已经得到了广泛的报道。尽管许多研究已经证实了它作为一种抗炎剂的安全性和疗效，但雷公藤红素对骨关节炎（OA）的影响尚不清楚。在这项研究中，我们发现雷公藤红素可预防手术性内侧半月板切除术（DMM）小鼠模型中的 OA 发展。此外，雷公藤红素抑制了人单核细胞系 THP-1 中 DMM 诱导和 LPS 诱导的促炎细胞因子的表达。进一步的机制研究表明，雷公藤红素通过上调核苷酸结合寡聚结构域样受体家族pyrin 结构域包含蛋白 3（NLRP3）和下调半胱天冬酶-1 来减少促炎细胞因子。最后，我们确定 hsa-miR-20b，一种靶向 NLRP3 基因的 microRNA，被雷公藤红素下调。这项研究为雷公藤红素在预防 OA 发病机制中的作用提供了新的见解。
