NLRP3 overexpression exacerbated synovium tissue degeneration in juvenile collagen-induced arthritis.

Juvenile idiopathic arthritis (JIA) can lead to synovial inflammation. JIA is a chronic autoimmune inflammatory condition that primarily affects children. It is recognized as the most prevalent form of arthritis in the pediatric population and is associated with significant impairment and disability. As an inflammatory regulator, Nod-like receptor 3 (NLRP3) has been implicated in various autoimmune diseases. However, the specific mechanism by which NLRP3 impacts the progress of JIA remains unclear. Therefore, we conducted this study to investigate the specific mechanism of NLRP3 on the progress of synovial inflammation in juvenile collagen-induced arthritis (CIA). The CIA model was established using Sprague‒Dawley (SD) rats aged 2-3 weeks. In this study, we investigated the potential role of NLRP3 on JIA by regulating the NLRP3-NF-κB axis in CIA rats. To verify the effect of NLRP3 on JIA, the expression of NLRP3 was knocked down or overexpressed by an adeno-associated virus injected into the knee joint of the CIA rats. In this study, we observed that NLRP3 plays an important role in the development of juvenile CIA, and knocking down NLRP3 inhibited inflammation and alleviated synovium inflammation. We also demonstrated that the expression of NLRP3 was increased in synovial tissue, and NLRP3 could upregulate the NF-κB signal pathway and influence inflammation. Moreover, we also found that increases in the expression of NLRP3 impairs autophagy capacity and increases activation of the pyroptosis pathway in the synovium of the juvenile CIA rats. The results demonstrated that NLRP3 interferes with synovial inflammation in juvenile CIA. These results provide new insight into the mechanism by which NLRP3 impacts the development of JIA and suggest that targeting the NLRP3 inflammasome may represent a promising therapeutic strategy for managing JIA.