目前尚无可改善OA病情的药物。明确OA发病机制可能为其治疗提供靶点。我们前期研究发现膝OA软骨细胞TTP表达减少并可能通过上调NLRP3诱导软骨细胞焦亡；滑膜炎滑膜外泌体可通过其升高的miR-27a-3p减少软骨细胞TTP促进其焦亡，而软骨细胞焦亡又可增加共孵育滑膜其外泌体中的miR-27a-3p。基于此我们提出假说：膝OA软骨细胞中低表达的TTP对NLRP3的mRNA降解减少导致软骨细胞焦亡，而炎症性滑膜其外泌体中的miR-27a-3p通过减少软骨细胞TTP诱导软骨细胞焦亡，焦亡的软骨细胞又可导致滑膜炎症并增加滑膜外泌体中的miR-27a-3p从而形成正反馈促进膝OA进展。本课题拟通过RNAi、荧光素酶报告实验及RIP等实验技术研究①TTP通过NLRP3对软骨细胞焦亡的调控；②滑膜外泌体miR-27a-3p介导的软骨细胞焦亡与滑膜炎症间的促OA正反馈互作，从而为膝OA的靶向治疗提供线索。

At present, there are no drugs to slow osteoarthritis (OA) progression. Clarifying the pathogenesis of OA may provide targets for its treatment. Our previous study found that tristetraprolin (TTP) decreased in knee OA chondrocytes and may induce chondrocyte pyroptosis by up-regulating NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3); increased miR-27a-3p in exosomes derived from synovium with synovitis can induce chondrocyte pyroptosis by down-regulate its TTP, and chondrocyte pyroptosis can increase miR-27a-3p in exosomes derived from co-incubated synovium. Based on this, we hypothesized that the low expressed TTP in knee OA chondrocyte reduces the degradation of NLRP3 mRNA and thereby induce chondrocyte pyroptosis, and miR-27a-3p in exosomes derived from synovium with synovitis reduce TTP in chondrocytes to induce it pyroptosis, and pyroptosis of chondrocytes can cause synovitis and increase miR-27a-3p in synovium derived exosomes, thus forming a vicious circle to promote the development of knee OA. This research aims to use experimental techniques such as RNA interference (RNAi), luciferase reporter assay, RNA immunoprecipitation, etc. to study ① the regulation of TTP on chondrocyte pyroptosis through NLRP3; ② the OA promoting positive feedback interaction between chondrocyte pyroptosis and synovitis mediated by miR-27a-3p of synovium derived exosomes, thus provide clues for targeted treatment of knee OA.