{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:17:15Z","timestamp":1779380235903,"version":"3.53.1"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600856"],"award-info":[{"award-number":["81600856"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201109"],"award-info":[{"award-number":["82201109"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>There is little knowledge about oxidative stress\u2010induced senescence involvement in apical periodontitis. Here, we explored its molecular mechanism in periapical lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ten cases of radicular cysts and five cases of periapical granulomas were randomly selected. Immunohistochemical analysis was performed to detect the expression and correlation between Senescence\u2010associated factor polymerase I and transcript release factor (PTRF) and Akt\/FoxO1 signaling. Human periodontal ligament cells (hPDLCs) pretreated with LY294002 were exposed to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced oxidative stress conditions and then cell proliferation, senescence, apoptosis, and associated signaling were evaluated by EdU labeling, \u03b2\u2010galactosidase assay, RT\u2010qPCR, and western blot analysis, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Polymerase I and transcript release factor and Akt\/FoxO1 signaling were more frequently expressed in the radicular cyst than in periapical granulomas. Notably, cells in radicular cysts showed Akt activation, FoxO1 phosphorylation, and cytoplasmic translocation. In vitro, prominent H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced senescence was observed in hPDLCs. LY294002, a PI3K inhibitor, attenuated the expression levels of senescence (Klotho, P16INK4), apoptosis (Bad, Fas), phosphorylated Akt, and phosphorylated FoxO1; however, did not affect cell proliferation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data indicated that senescence is present in clinical periapical lesions, and Akt\/FoxO1 signaling is involved in the H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced cellular senescence, which could serve as a potential therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.14703","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T12:36:45Z","timestamp":1690979805000},"page":"2463-2472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The roles of stress\u2010induced premature senescence and Akt\/<scp>FoxO1<\/scp> signaling in periapical lesions"],"prefix":"10.1111","volume":"30","author":[{"given":"Qian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"School of Stomatology, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"School of Stomatology, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration  Wuhan 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