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Conversely, cartilage-specific overexpression of GPX4 via transgenic technology, or restoration of its activity using small molecule drugs such as certain natural compounds or ferroptosis inhibitors, can significantly delay cartilage degeneration, improve subchondral bone sclerosis and osteophyte formation, and alleviate synovitis in model animals (Xiao et al., 2024), which directly confirms the protective role of GPX4 in OA progression from a gain-of-function perspective

Manganese induces the mitochondrial permeability transition in cultured astrocytes

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