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NK cells can eliminate abnormal joint cells or pathogens via perforin and granzymes, and they secrete cytokines such as IFN- and TNF- to regulate immunity and inflammation ( 4.2 Regulation of ferroptosis by inflammatory cytokines and immune signaling 4.2.1 Classic proinflammatory cytokines IL-1 can induce the synthesis of matrix-degrading enzymes MMP-13 and ADAMTS-5 by chondrocytes and synovial cells ( Apart from exacerbating local inflammation, TNF- can activate the NF-KB and MAPK signaling pathways, increasing cellular susceptibility to oxidative stress and weakening GPX4 and other antioxidant enzymes, thereby promoting further accumulation of lipid peroxidation byproducts and markedly elevating ferroptosis risk ( As noted earlier, IL-6 is often significantly upregulated in the synovial fluid and serum of OA patients