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

Abstract

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. <i>In vitro</i> 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-<i>α</i> (TNF-<i>α</i>), and interleukin-1<i>β</i> (IL-1<i>β</i>), indicating its anti-inflammatory effects. <i>In vivo</i> 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.