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Vitexin, a natural flavonoid with diverse pharmacological activities, has recently attracted attention for its potential protective effects against OA. This study investigated whether Vitexin alleviates OA progression through regulation of Sirtuin 3 (SIRT3)\u2010mediated ferroptosis and mitochondrial dysfunction in chondrocytes. In\u00a0vitro, erastin\u2010induced rat chondrocytes were treated with Vitexin to evaluate ferroptosis, oxidative stress, and mitochondrial function. In\u00a0vivo, a rat OA model was established to assess the protective effects of Vitexin on cartilage degeneration and subchondral bone destruction. Vitexin markedly reduced iron accumulation, lipid peroxidation, and reactive oxygen species generation while restoring mitochondrial function and redox homeostasis in chondrocytes. Moreover, Vitexin upregulated SIRT3, GPX4, and xCT expression, whereas SIRT3 knockdown partially abolished these protective effects. In\u00a0vivo analyses further demonstrated that Vitexin attenuated cartilage degeneration, preserved subchondral bone architecture, and restored SIRT3 and GPX4 expression in OA rats. Collectively, these findings demonstrate that Vitexin alleviates OA progression through SIRT3\u2010mediated inhibition of chondrocyte ferroptosis and mitochondrial dysfunction, highlighting its potential as a novel therapeutic strategy for OA.<\/jats:p>","DOI":"10.1002\/ptr.70410","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:03:52Z","timestamp":1782194632000},"page":"5551-5565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vitexin Alleviates Osteoarthritis Progression Through Sirtuin 3\u2010Mediated Inhibition of Chondrocyte Ferroptosis and Mitochondrial Dysfunction"],"prefix":"10.1002","volume":"40","author":[{"given":"Boyu","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Spine Surgery Shenzhen Pingle Orthopedic Hospital (Shenzhen Pingshan Traditional Chinese Medicine Hospital)  Shenzhen China"},{"name":"Department of Orthopaedics Dongguan 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