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 RuO 2 (d-RuO 2 ) as an effective antioxidant for the treatment of OA. Unlike the crystalline RuO 2, the amorphous hydrous RuO 2 nanospheres (composed of self-assembled ultrasmall RuO 2 ) displayed superior nanozymatic antioxidant activities. In vitro studies demonstrated that d-RuO 2 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-1 β (IL-1 β ), indicating its anti-inflammatory effects. In vivo experiments showed that d-RuO 2 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-RuO 2 attenuated the progression of OA by suppressing the ROS/NLRP3/Caspase-1 signaling pathway. In conclusion, we presented d-RuO 2 as an efficient ROS scavenger, providing a potential therapeutic strategy for OA.