{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:37:05Z","timestamp":1789533425319,"version":"build-2803163510"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research and Development Program of Luzhou Science and Technology Bureau in 2022","award":["Project No. 2022-SYF-76"],"award-info":[{"award-number":["Project No. 2022-SYF-76"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Ferroptosis is a nonapoptotic form of cell death characterized by lipid peroxidation and intracellular iron accumulation. OA is a prevalent joint disease, and as OA progresses, inflammation or iron overload can induce ferroptosis in chondrocytes. However, research on genes that play important roles in this process remains insufficient.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>In this study, we identified the ferroptosis-related gene SAT1 by analyzing OA-associated GEO datasets. For <jats:italic><jats:italic>in vivo<\/jats:italic><\/jats:italic> experiments, we induced an OA mouse model by transecting the medial meniscus ligament. <jats:italic><jats:italic>In vitro<\/jats:italic><\/jats:italic>, we analyzed the biological functions of SAT1 in ATDC5 cells using Cell Counting Kit-8 (CCK-8), trypan blue staining, Western blot, and detection of ferroptosis-related indicators. Additionally, we explored the mechanisms underlying SAT1\u2019s role in OA progression through immunoblotting, ubiquitination, and acetylation immunoprecipitation experiments.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Bioinformatics analysis revealed a close association between OA and ferroptosis. Our experimental results showed that overexpression of SAT1 effectively induced ferroptosis in ATDC5 cells. Mechanistically, SAT1 promoted p53 stability by downregulating TRIM33, which inhibits p53 acetylation. By suppressing TRIM33 expression, SAT1 enhanced p53 acetylation and stability, thereby increasing ferroptosis and exacerbating OA progression.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In summary, our data indicate that SAT1 is a potential key gene in OA, revealing the crucial role of the SAT1-TRIM33-p53 axis in OA pathogenesis. This axis promotes ferroptosis by enhancing p53 acetylation, suggesting that targeting SAT1 may represent a novel therapeutic strategy for improving OA.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0332761","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:36:51Z","timestamp":1759945011000},"page":"e0332761","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["SAT1 promotes the progression of OA by regulating TRIM33-mediated p53 acetylation to enhance 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