Molybdenum nanoclusters as potent antioxidants for the treatment of osteoarthritis.

Osteoarthritis (OA) is a debilitating degenerative joint disease characterized by chronic inflammation, in which oxidative stress plays a pivotal role in shaping the inflammatory microenvironment. Interrupting the vicious cycle driven by excessive reactive oxygen species (ROS) and proinflammatory mediators is therefore critical for effective OA therapy. In this study, we developed molybdenum nanoclusters (MNs) as novel nano-antioxidants with strong ROS-scavenging ability for OA protection. MNs efficiently eliminate ROS, alleviate oxidative stress-induced chondrocyte injury, inhibit apoptosis, and suppress the production of inflammatory cytokines. Moreover, MNs modulated the immune microenvironment by reprogramming macrophages from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype. An in vivo OA mouse model was established via destabilization of the medial meniscus (DMM), and MNs treatment effectively prevented and even reversed OA progression by restoring redox balance and promoting M2-dominant macrophage polarization in the synovium. Collectively, these findings demonstrate that MNs serve as safe and multifunctional nano-antioxidants with dual redox-regulatory and immunomodulatory effects, suggesting a promising therapeutic strategy for OA and other inflammation-related diseases associated with oxidative stress.