{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:07:08Z","timestamp":1789578428415,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515030015"],"award-info":[{"award-number":["2024A1515030015"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies have shed light on the important role of aging in the pathogenesis of joint degenerative diseases and the anti\u2010aging effect of alpha\u2010ketoglutarate (\u03b1KG). However, whether \u03b1KG has any effect on temporomandibular joint osteoarthritis (TMJOA) is unknown. Here, we demonstrate that \u03b1KG administration improves condylar cartilage health of middle\u2010aged\/aged mice, and ameliorates pathological changes in a rat model of partial discectomy (PDE) induced TMJOA. In\u00a0vitro, \u03b1KG reverses IL\u20101\u03b2\u2010induced\/H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced decrease of chondrogenic markers (<jats:italic>Col2<\/jats:italic>, <jats:italic>Acan<\/jats:italic> and <jats:italic>Sox9<\/jats:italic>), and inhibited IL\u20101\u03b2\u2010induced\/ H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced elevation of cartilage catabolic markers (<jats:italic>ADAMTS5<\/jats:italic> and <jats:italic>MMP13<\/jats:italic>) in condylar chondrocytes. In addition, \u03b1KG downregulates senescence\u2010associated (SA) hallmarks of aged chondrocytes, including the mRNA\/protein level of SA genes (<jats:italic>p16<\/jats:italic> and <jats:italic>p53<\/jats:italic>), markers of nuclear disorders (Lamin A\/C) and SA\u2010\u03b2\u2010gal activities. Mechanically, \u03b1KG decreases the expressions of p\u2010IKK and p\u2010NF\u2010\u03baB, protecting TMJ from inflammation and senescence\u2010related damage by regulating the NF\u2010\u03baB signaling. Collectively, our findings illuminate that \u03b1KG can ameliorate age\u2010related TMJOA and PDE\u2010induced TMJOA, maintain the homeostasis of cartilage matrix, and exert anti\u2010aging effects in chondrocytes, with a promising therapeutic potential in TMJOA, especially age\u2010related TMJOA.<\/jats:p>","DOI":"10.1111\/acel.14269","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T06:15:30Z","timestamp":1720764930000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Alpha\u2010ketoglutarate ameliorates age\u2010related and surgery induced temporomandibular joint osteoarthritis via regulating <scp>IKK<\/scp>\/<scp>NF<\/scp>\u2010<scp>\u03baB<\/scp> signaling"],"prefix":"10.1111","volume":"23","author":[{"given":"Xiaoping","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou 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