Chondroitin Sulfate A-Selenium Nanoparticles Activate Autophagy Through the AMPK-mTOR Pathway to Alleviate Oxidative Stress and Mitochondrial Dysfunction to Repair Kashin-Beck Disease Chondrocytes

Kashin-Beck disease (KBD) is a chronic osteoarticular disease. Chondroitin sulfate A-selenium nanoparticles (CSA-SeNP), a polysaccharide-based nanoparticle, have shown promise in facilitating cartilage repair, but the mechanism remains unclear. Given our previous findings of downregulated AMPK-mTOR pathway and autophagy in KBD chondrocytes, this study explored the effects of CSA-SeNP on the AMPK-mTOR pathway and autophagy levels in KBD chondrocytes. KBD chondrocytes were treated with CSA-SeNP and AMPK inhibitors alone or in combination. We found that CSA-SeNP promoted autolysosome content and autophagic flux and upregulated the AMPK-mTOR pathway and autophagy markers, while reducing apoptosis in KBD chondrocytes. It effectively alleviated oxidative stress, as evidenced by decreased ROS level and MDA concentration, along with increased activities of antioxidant enzymes (SOD, CAT, and T-AOC). Concurrently, it also improved mitochondrial function, including elevated ATP content, enhanced SDH and ATPase activities, and restored mitochondrial membrane potential. However, co-treatment of KBD chondrocytes with CSA-SeNP and AMPK inhibitor resulted in levels of autolysosome content, autophagic flow, AMPK-mTOR pathway activity, autophagy markers, apoptosis, oxidative stress, and mitochondrial function that were intermediate between those observed with respective treatment with CSA-SeNP or AMPK inhibitor. In summary, CSA-SeNP could effectively activate AMPK-mTOR pathway to promote autophagy process, reduce oxidative stress and apoptosis, and improve mitochondrial function, thereby repairing KBD chondrocytes. This study may provide new insights into the potential of CSA-SeNP as a therapeutic agent for KBD.