{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:21:45Z","timestamp":1793060505557,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ60025"],"award-info":[{"award-number":["2023JJ60025"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,8,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteoarthritis (OA) is a common joint disease, and chondrocyte extracellular matrix (ECM) degradation was closely associated with its progression. This study investigated the regulatory mechanisms of ECM degradation during OA development. A rat model of OA was established by anterior cruciate ligament transection (ACL\u2010T) and interleukin\u20101 beta (IL\u20101\u03b2)\u2010stimulated rat chondrocytes were used to simulate OA in\u00a0vitro. Cartilage damage was evaluated by hematoxylin\u2013eosin (HE) and safranin O\u2010fast green staining. The ECM content in chondrocytes was assessed by alcian blue staining. Real\u2010time quantitative PCR (RT\u2010qPCR), Western Blotting, immunohistochemical staining, and immunofluorescent staining were adopted to analyze associated molecule expression. Molecular mechanisms were elucidated by Co\u2010immunoprecipitation (Co\u2010IP) and GST pull\u2010down assay. We found that Aurora kinase A (AURKA), p\u2010eukaryotic translation initiation factor 4E (eIF4E), and ADAM metallopeptidase with thrombospondin type 1 motif 12 (ADAMTS12) levels were elevated in the human and rat cartilage tissues of OA, as well as IL\u20101\u03b2\u2010exposed chondrocytes. AURKA inhibition restrained ECM degradation to relieve OA via down\u2010regulation of ADAMTS12. AURKA overexpression phosphorylated eIF4E, which promoted cap\u2010dependent translation of ADAMTS12. Moreover, DNA methyltransferase 1 (DNMT1)\u2010mediated methylation down\u2010regulated HECT domain E3 ubiquitin protein ligase 1 (HECTD1) in the OA model and consequently enhanced AURKA expression via inhibiting its ubiquitination. HECTD1 knockdown or ubiquitination repression intensified ECM degradation in IL\u20101\u03b2\u2010stimulated chondrocytes. Taken together, low expression of HECTD1 repressed AURKA ubiquitination to elevate AURKA protein level and subsequently facilitated eIF4E\u2010mediated cap\u2010dependent translation of ADAMTS12, thus resulting in ECM degradation during OA progression.<\/jats:p>","DOI":"10.1096\/fj.202500241r","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T10:40:09Z","timestamp":1755772809000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inflammation Inhibits\n                    <scp>HECTD1<\/scp>\n                    \u2010Mediated\n                    <scp>AURKA<\/scp>\n                    Ubiquitination to Cause Extracellular Matrix Degradation in Osteoarthritis via Enhancing Cap\u2010Dependent\n                    <scp>mRNA<\/scp>\n                    Translation of\n                    <scp>ADAMTS12<\/scp>"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9925-3264","authenticated-orcid":false,"given":"Duo","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Orthopedics Hunan Provincial People's Hospital (The First\u2010Affiliated Hospital of Hunan Normal University)  Changsha Hunan Province People's Republic of China"},{"name":"Clinical Research Center of Sports Medicine in Hunan Province  Changsha Hunan Province People's Republic of China"},{"name":"Hunan Provincial Engineering Research Center for Precision Diagnosis Treatment and Rehabilitation of Joints and Sports Medicine With Chinese and Western Medicine  Changsha Hunan Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Hunan Provincial People's Hospital (The First\u2010Affiliated Hospital of Hunan Normal 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