{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:02:47Z","timestamp":1777492967636,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T00:00:00Z","timestamp":1755302400000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Osteoarthritis (OA) is a common degenerative disease involving pathological changes in joint tissues, which seriously affects the quality of life of patients. It was reported that both Cyclin dependent kinase inhibitor 1A (CDKN1A) and ubiquitinating enzyme MDM2 exhibited abnormal expression in OA. However, it is currently unclear whether there is a specific regulatory mechanism between the two.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Firstly, C28\/I2 cells were treated with IL\u20101\u03b2 to construct an in\u00a0vitro cell model of OA, while qRT\u2010PCR and western blot were used to detect the mRNA and protein levels of CDKN1A and MDM2. C28\/I2 cell viability, apoptosis, and the release of inflammatory factors were measured by CCK\u20108, flow cytometry, and ELISA kits. In addition, the levels of Fe<jats:sup>2+<\/jats:sup>, glutathione (GSH), reactive oxygen species (ROS), and Malondialdehyde (MDA) were evaluated by corresponding kits. Subsequently, the relationship between MDM2 and CDKN1A was predicted by the UbiBrowser website, and the ubiquitination level of CDKN1A and the interaction between them were verified by western blot and Co\u2010IP technology. Cycloheximide (CHX) exposure was used to assess mRNA stability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CDKN1A was downregulated in OA cartilage tissues and IL\u20101\u03b2 induced C28\/I2 cells, while overexpression of CDKN1A enhanced C28\/I2 cell activity and inhibited cell apoptosis. Meanwhile, the release of IL\u20106 and TNF\u2010\u03b1 as well as ferroptosis and oxidative stress, were also hindered by CDKN1A overexpression. MDM2 was highly expressed in OA patients and in IL\u20101\u03b2 induced C28\/I2 cells and mediated the ubiquitination modification of CDKN1A. Most importantly, MDM2 knockdown alleviated IL\u20101\u03b2\u2010induced chondrocyte damage via upregulating CDKN1A.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MDM2 downregulated the level of CDKN1A in chondrocytes by mediating the ubiquitination modification of CDKN1A, leading to impaired chondrocyte viability and inducing ferroptosis and oxidative stress.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.70384","type":"journal-article","created":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T02:59:45Z","timestamp":1755399585000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ubiquitin Ligase <scp>MDM2<\/scp> Regulates Chondrocyte Damage, Ferroptosis, and Oxidative Stress by Modulating the Ubiquitination Level of <scp>CDKN1A<\/scp>"],"prefix":"10.1111","volume":"28","author":[{"given":"Kaihong","family":"Gui","sequence":"first","affiliation":[{"name":"Department of Orthopedics 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