FGF21 and metabolic disease: Studies show that metabolic disorders and increased ECM catabolism in articular cartilage are key factors in OA development.135 Guo et al. studied the relationship between mitochondrial DNA dysfunction and OA, finding that STING activates the NF-κB signaling cascade to promote senescence, inducing secondary ECM degradation in OA.136 Lu et al. demonstrated that fibroblast growth factor 21 (FGF21) alleviates chondrocyte senescence and ECM impairment in OA via the SIRT1-mTOR signaling pathway.137 FGF21 administration has been shown to alleviate both chondrocyte senescence and ECM catabolism.