CAT/SOD-Enriched Achyranthes bidentata nanovesicles mitigate TMJOA via ROS scavenging and JNK/FOXO1 pathway Inhibition.

Temporomandibular joint osteoarthritis (TMJOA) is an inflammatory disorder with limited treatment options. Given the key role of oxidative stress in TMJOA progression, targeting this pathway may offer therapeutic benefits. In this study, we isolated and characterized exosome-like nanovesicles from Achyranthes bidentata (ABNVs), a traditional Chinese herb known for its antioxidant properties. ABNVs exhibited an average size of 134.7 nm and a negatively charged surface (-30.32 mV), and were enriched with antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). In a rat TMJOA model, ABNVs (1 µg/mL) effectively reduced cartilage degradation, bone damage, and synovial inflammation while maintaining high biocompatibility. Immunohistochemical analysis revealed that ABNVs suppressed M1 macrophage polarization. In vitro, ABNVs did not impair chondrogenic differentiation but mitigated chondrocyte inflammation. Mechanistically, ABNVs scavenged reactive oxygen species (ROS) and reduced macrophage inflammation through CAT/SOD-mediated ROS clearance and modulation of the JNK/FOXO1 pathway. Additionally, ABNVs indirectly enhanced chondrogenic differentiation by inhibiting M1 macrophage activation. Our findings demonstrate that ABNVs hold promise as a therapeutic strategy for TMJOA by targeting oxidative stress and inflammation via ROS scavenging and JNK/FOXO1 regulation.