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These mediators diffuse through the synovial fluid to the cartilage surface, where they drive chondrocytes toward catabolic, hypertrophic, or senescent phenotypes, upregulate MMPs and aggrecanases, suppress COL2A1 and ACAN expression, and promote oxidative stress and ferroptosis, thereby accelerating ECM breakdown (Wang et al., 2022)

10.1111/jnc.13361 23 CockH

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For example, deletion of atfs-1 , which is required for induction of the UPR mt , fails to impede lifespan extension caused by certain specific UPR mt inducer genes 15