Electroacupuncture delays the progression of juvenile collagen-induced arthritis via regulation NLRP3/ NF-κB signaling pathway -mediated pyroptosis and its influence on autophagy.

Abstract

Background: 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. Electroacupuncture (EA) effectively treats various synovium-related conditions, including symptoms of synovial inflammation, in both human and animal models. However, the specific mechanism by which EA protects against JIA remains unclear. Therefore, we conducted a comprehensive study to investigate the protective mechanisms of EA in a rat model. We aimed to examine the impact of EA on pathological changes in synovial tissue of juvenile collagen-induced arthritis (CIA) rats.

Methods: The CIA model was established using Sprague‒Dawley (SD) rats aged 2-3 weeks. In this study, we investigated the potential role of EA on JIA by regulating the NLRP3-NF-κB axis in juvenile CIA rats and its influence on autophagy. To verify the effect of EA on juvenile CIA, the expression of NLRP3 was overexpressed by an adeno-associated virus injected into the knee joint of the CIA rats.

Results: In this study, we observed that NLRP3 plays an important role in developing juvenile CIA and that NLRP3 overexpression exacerbates inflammation and increases 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 increases in the expression of NLRP3 by impairing autophagy capacity and activation of the pyroptosis pathway in the synovium of the juvenile CIA rats.

Conclusion: Moreover, we also discovered that EA decreased the expression of NLRP3 by restoring the impaired autophagy capacity and inhibiting the NLRP3-NF-κB axis, thereby delaying the progression of juvenile CIA. These results showed that EA is effective in inhibiting inflammation and synovial degeneration and alleviating the progression of juvenile CIA. As a result, our results provide new insight into the mechanism by which EA delays the development of juvenile CIA, offering a novel therapeutic regimen for JIA. This trial was registered with ClinicalTrials.gov, number NCT10203935. Registered October 07, 2023. Key Points • NLRP3 plays a critical role in juvenile collagen-induced arthritis (CIA), with its overexpression linked to increased inflammation in synovial tissue. • Electroacupuncture (EA) reduces NLRP3 expression and inhibits the NLRP3-NF-κB axis, mitigating inflammatory responses and delaying juvenile CIA progression. • EA restores impaired autophagy in juvenile CIA rats, promoting cellular health and inflammation management. • EA alleviates synovial degeneration, improving joint health and function in juvenile CIA models.