Mitigating Oxidative Stress Enhances Cartilage Regeneration by Ameliorating Apoptosis of Cartilage Progenitor Cells in Adult Mice

AbstractCartilage regeneration in juvenile mice was better than in adult mice. This study evaluated the roles of cytokines and reactive oxygen species (ROS) after cartilage injury in both juvenile and adult mice and attempted to correlate these with cartilage progenitor cells and age‐related differences in cartilage regeneration. Full‐thickness cartilage defects were created in the femoral trochlea of knee joints in both 4‐week‐old (juvenile) and 8‐week‐old (adult) mice. Adult mice showed higher ROS peaks than juveniles at day 7 post‐injury. Protein expression levels of tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) significantly decreased after surgery, while interleukin‐1β (IL‐1β) levels displayed no significant change. There were more cartilage progenitor cells together with more cell proliferation in juvenile versus adult mice, while there was much less apoptosis of cartilage progenitor cells in juvenile mice compared to adult mice. ROS inhibition enhanced cartilage regeneration in adult mice by promoting progenitor cell proliferation and reducing apoptosis, mimicking the regenerative pattern seen in juveniles. This study demonstrated that inhibiting ROS in adult mice promoted cartilage regeneration, possibly by enhancing proliferation and decreasing apoptosis of cartilage progenitor cells.