Osteoarthritis (OA) is an age-related chronic joint degenerative disease. Interleukin 1 beta (IL-1β) is considered a marker for the progression of OA. In this study, we found that Ubiquitin-Specific Peptidase 49 (USP49) was significantly less expressed in OA patients compared with healthy individuals. Treating primary rat chondrocytes with different concentrations of IL-1β resulted in decreased Usp49 expression, while Usp49 overexpression could attenuate IL-1β-induced chondrocyte apoptosis by promoting Axin deubiquitination. The deubiquitination of Axin led to the accumulation of the protein, which in turn resulted in β-catenin degradation and Wnt/β-catenin signaling cascade inhibition. Interestingly, we also found that [6]-gingerol, an anti-OA drug, could upregulate the protein level of Usp49 and suppress the Wnt/β-catenin signaling cascade in primary rat chondrocytes. Taken together, our study not only demonstrates that Usp49 can negatively regulate the progression of OA by inhibiting the Wnt/β-catenin signaling cascade, but also elucidates the underlying molecular mechanisms.

骨关节炎（OA）是一种与年龄有关的慢性关节退行性疾病。白介素1 beta（IL-1β）被认为是OA进展的标志。在这项研究中，我们发现泛素特异性肽酶49（USP49）在OA患者中的表达明显低于健康个体。用不同浓度的IL-1β处理大鼠原代软骨细胞会导致Usp49表达降低，而Usp49过表达可以通过促进Axin去泛素化来减弱IL-1β诱导的软骨细胞凋亡。Axin的去泛素化导致蛋白质的积累，进而导致β-catenin降解和Wnt /β-catenin信号级联抑制。有趣的是，我们还发现抗OA药物[6]-姜油酚可以上调Usp49的蛋白水平并抑制原代大鼠软骨细胞中的Wnt /β-catenin信号级联。两者合计，我们的研究不仅表明Usp49可以通过抑制Wnt /β-catenin信号级联反应负调控OA的进程，而且阐明了潜在的分子机制。