Defective RuO2 Nanospheres Attenuate Osteoarthritis Progression via Suppressing the ROS/NLRP3/Caspase-1 Signaling Pathway

Osteoarthritis (OA) is the most prevalent degenerative joint disorder, characterized by chronic inflammation, cartilage degeneration, and the formation of osteophytes, which leads to serious economic and social challenges. Previous studies have demonstrated that oxidative stress-driven inflammation plays a crucial role in the pathophysiological progression of OA. In this study, we presented defective RuO2 (d-RuO2) as an effective antioxidant for the treatment of OA. Unlike the crystalline RuO2, the amorphous hydrous RuO2 nanospheres (composed of self-assembled ultrasmall RuO2) displayed superior nanozymatic antioxidant activities. In vitro studies demonstrated that d-RuO2 significantly reduced intracellular levels of reactive oxygen species (ROS), and decreased the expression of key inflammatory markers including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), indicating its anti-inflammatory effects. In vivo experiments showed that d-RuO2 effectively relieved pain, improved physical activity, and mitigated synovitis, cartilage degeneration, and bone remodeling induced by destabilization of the medial meniscus (DMM). Furthermore, the mechanistic investigations indicated that d-RuO2 attenuated the progression of OA by suppressing the ROS/NLRP3/Caspase-1 signaling pathway. In conclusion, we presented d-RuO2 as an efficient ROS scavenger, providing a potential therapeutic strategy for OA.