{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:28:23Z","timestamp":1773926903334,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteoarthritis (OA), marked by articular cartilage degeneration, severely impairs joint function. Ubiquitin\u2010specific peptidase 16 (USP16) is crucial for regulating cellular protein stability and signaling pathways. This study seeks to elucidate USP16's impact and mechanism on chondrocyte injury in OA. The expression of USP16 in OA was analyzed using the Gene Expression Omnibus (GEO) database. An in vitro model using IL\u20101\u03b2 to induce OA\u2010like conditions. Real\u2010time quantitative PCR (RT\u2010qPCR) and western blot were used to detect gene expression in tissues and cells. The cellular oxidative stress levels were assessed using cell metabolism kits specifically targeted at reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Enzyme\u2010linked immunosorbent (ELISA) assays were conducted to detect the levels of interleukin\u20106 (IL\u20106) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) in cell culture supernatants and serum, thereby evaluating the inflammatory response state. The apoptotic status of the cells was detected by flow cytometry. The Ubibrowser website was used to predict proteins that interact with USP16. Co\u2010immunoprecipitation (CoIP) and GST pull\u2010down experiments were conducted to validate the interaction between USP16 and POU class 2 homeobox 1 (POU2F1). The cycloheximide (CHX) chase assay was utilized to determine the half\u2010life of proteins. Mouse models of OA were established for in vivo validation, and the degree of cartilage degeneration was assessed through hematoxylin\u2013eosin (HE) staining. USP16 expression was found to be reduced in OA patients and in HACCs induced by IL\u20101\u03b2. The induction of IL\u20101\u03b2 led to an increase in oxidative stress levels in human articular chondrocyte cells (HACCs), accelerated the inflammatory response and the rate of apoptosis within HACCs, and inhibited the normal expression of chondrogenesis\u2010related proteins in HACCs. However, overexpressing USP16 was able to alleviate these adverse effects. Furthermore, USP16 interacted with POU2F1 and stabilized its expression by means of deubiquitination. Notably, when POU2F1 was knocked down, the protective effect of overexpressing USP16 on IL\u20101\u03b2\u2010induced HACCs was significantly weakened. In vivo experiments demonstrated that overexpressing USP16 effectively inhibited the degenerative process of mouse cartilage, significantly lowered the Osteoarthritis Research Society International (OARSI) and Mankin scores in mice, decreased oxidative stress levels, and suppressed inflammatory responses. USP16 regulates chondrocyte damage in OA by exerting its deubiquitination role to stabilize the POU2F1 protein, providing a potential target and theoretical foundation for OA treatment.<\/jats:p>","DOI":"10.1002\/jbt.70773","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:21:13Z","timestamp":1773033673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ubiquitin\u2010Specific Peptidase 16 Alleviates Chondrocyte Damage in Osteoarthritis Through Deubiquitinating and Stabilizing POU Class 2 Homeobox 1"],"prefix":"10.1002","volume":"40","author":[{"given":"Wei","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Rehabilitation, Jiangxi Provincial People's Hospital The First Affiliated Hospital of Nanchang Medical College Nanchang China"},{"name":"Department of Rehabilitation, Xiangya Hospital (National Regional Center for Neurological Diseases) Central South University Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Jiangxi Provincial People's Hospital The First Affiliated Hospital of Nanchang Medical College Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sixie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Jiangxi Provincial People's Hospital The First Affiliated Hospital of Nanchang Medical College Nanchang China"},{"name":"Department of Rehabilitation, Xiangya Hospital (National Regional Center for Neurological Diseases) Central South University Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zebu","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Jiangxi Provincial People's Hospital The First Affiliated Hospital of Nanchang Medical College Nanchang China"},{"name":"Department of Rehabilitation, Xiangya Hospital (National Regional Center for Neurological Diseases) Central South University Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianxiang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Jiangxi Provincial People's Hospital The First Affiliated Hospital of Nanchang Medical College Nanchang China"},{"name":"Department of Rehabilitation, Xiangya Hospital (National Regional Center for Neurological Diseases) Central South University Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanru","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Jiangxi Provincial People's Hospital The First Affiliated Hospital of Nanchang Medical College Nanchang China"},{"name":"Department of Rehabilitation, Xiangya Hospital (National Regional Center for Neurological Diseases) Central South University Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanxiang","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Jiangxi Provincial People's Hospital The First Affiliated Hospital of Nanchang Medical College Nanchang China"},{"name":"Department of Rehabilitation, Xiangya Hospital (National Regional Center for Neurological Diseases) Central South University Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6562-5589","authenticated-orcid":false,"given":"Yuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Xiangya Hospital (National Regional Center for Neurological Diseases) Central South University Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-025-00594-6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-018-4270-4"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-023-03006-w"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052619"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-023-01223-y"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0257507"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2024.07.014"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2024.2391524"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.7326\/ANNALS-24-01249"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2021.11.015"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.07.038"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-020-00702-6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2315163120"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.20-043"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac468"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201502044"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12060886"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-024-01342-2"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41800-x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-34562-w"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01964-6"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.66037"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-023-03095-7"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc4009"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107150"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2021.110074"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20102493"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.03.010"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.047027"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-023-04011-w"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2061"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-019-1747-y"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07895-3"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1319"},{"issue":"2","key":"e_1_2_9_36_1","first-page":"672","article-title":"\u201cPOU2F1 Induces the Immune Escape in Lung Cancer by Up\u2010Regulating PD\u2010L1,","volume":"13","author":"Li F.","year":"2021","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-02148-y"},{"issue":"8","key":"e_1_2_9_38_1","first-page":"1665","article-title":"\u201cPOU2F1 Promotes Growth and Metastasis of Hepatocellular Carcinoma Through the FAT1 Signaling Pathway,","volume":"7","author":"Zhu H. Y.","year":"2017","journal-title":"American Journal of Cancer Research"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-018-0734-0"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202412379"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.07.014"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-16585-6"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.220"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-01843-8"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1415-47572014000400002"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.10.006"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.91206"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.134629"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007687"},{"issue":"3","key":"e_1_2_9_50_1","first-page":"751","article-title":"Conserved POU\u2010Binding Site Linked to SP1\u2010Binding Site Within FZD5 Promoter: Transcriptional Mechanisms of FZD5 in Undifferentiated Human ES Cells, Fetal Liver\/Spleen, Adult Colon, Pancreatic Islet, and Diffuse\u2010Type Gastric Cancer","volume":"30","author":"Katoh Y.","year":"2007","journal-title":"International Journal of Oncology"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jshs.2022.10.004"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70773","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70773","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70773","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T10:02:30Z","timestamp":1773914550000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/jbt.70773"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70773","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-08-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70773"}}