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In contrast, human studies offer mixed results

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Using similar strategies for upstream positive regulators of GPX4, for example, upregulating SLC7A11 expression via gene therapy, can multi-targetedly enhance the cell’s overall antioxidant capacity and GSH supply, thereby indirectly supporting and enhancing GPX4 activity ( via intra-articular AAV-Gfi1 injection, inactivated the MAPK signaling pathway, subsequently observing downregulation of ferroptosis promoters such as Cox2 and Acsl4 and upregulation of ferroptosis inhibitors such as GPX4 and SLC7A11, ultimately alleviating cartilage degeneration, osteophyte formation, and synovitis, and improving OA progression (Table 2)