Rheumatoid arthritis (RA) is a prevalent inflammatory disorder affecting about 1% of the global population. The ubiquitin-specific protease 2 (USP2) is known to have a substantial influence on the regulation of several cellular processes. Both in vivo (using rats with collagen-induced arthritis, CIA) and in vitro (using human fibroblast-like synoviocytes, HFLS-RA) models of RA were used to examine the role of USP2 in RA. The proliferation of HFLS-RA cells was assessed using the cell counting kit 8 test and EdU staining. The technique used for the assessment of gene expression was quantitative real-time PCR. Protein expression was quantified using Western blot (WB) analysis, while the quantities of inflammatory factors and matrix metalloproteinases were assessed using an ELISA test. The co-immunoprecipitation and ubiquitination tests investigated the relationships between proteins and the underlying molecular pathways. The results of this study demonstrate an upregulation of USP2 expression in both vivo and vitro models of RA. In addition, our findings indicate that the overexpression of USP2 notably exacerbates both proliferation and inflammation. The consistent downregulation of USP2 resulted in a reduction in the secretion of inflammatory cytokines and a suppression of cellular proliferation. Furthermore, it was shown that USP2 interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2) and facilitates the removal of ubiquitination chains from TRAF2, enhancing its stability. Our findings propose that USP2 functions as a favorable modulator of proliferation and inflammatory reactions in HFLS-RA, thereby indicating its potential as a therapeutic target for the treatment of RA.

类风湿性关节炎 (RA) 是一种常见的炎症性疾病，影响全球约 1% 的人口。已知泛素特异性蛋白酶 2 (USP2) 对多种细胞过程的调节具有重大影响。RA 的体内（使用胶原诱导性关节炎大鼠，CIA）和体外（使用人成纤维样滑膜细胞，HFLS-RA）模型均用于检查 USP2 在 RA 中的作用。使用细胞计数试剂盒8测试和EdU染色评估HFLS-RA细胞的增殖。用于评估基因表达的技术是定量实时PCR。使用蛋白质印迹 (WB) 分析对蛋白质表达进行定量，同时使用 ELISA 测试评估炎症因子和基质金属蛋白酶的数量。免疫共沉淀和泛素化测试研究了蛋白质与潜在分子途径之间的关系。本研究的结果表明，在 RA 体内和体外模型中 USP2 表达均上调。此外，我们的研究结果表明 USP2 的过度表达显着加剧增殖和炎症。USP2 的持续下调导致炎症细胞因子分泌减少和细胞增殖抑制。此外，研究表明 USP2 与肿瘤坏死因子受体相关因子 2 (TRAF2) 相互作用，促进 TRAF2 泛素化链的去除，从而增强其稳定性。我们的研究结果表明，USP2 在 HFLS-RA 中充当增殖和炎症反应的有利调节剂，从而表明其作为 RA 治疗靶点的潜力。