{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:47:24Z","timestamp":1791859644331,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515010854"],"award-info":[{"award-number":["2021A1515010854"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2020A1515011455"],"award-info":[{"award-number":["2020A1515011455"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2020A1515110027"],"award-info":[{"award-number":["2020A1515110027"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Clinic Periodontology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Necroptosis participates in the pathogenesis of many inflammatory diseases, including periodontitis. Here, we aimed to investigate the role and mechanism of necroptosis inhibitors in attenuating periodontitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The Gene Expression Omnibus (GEO)\u00a0dataset GSE164241 was re\u2010analysed to identify the role of necroptosis in periodontitis. Gingival specimens from healthy subjects or periodontitis patients were collected to evaluate the expression level of necroptosis\u2010associated proteins. The therapeutic effect of necroptosis inhibitors on periodontitis was assessed in vivo and in vitro. Moreover, Transwell assays and Western blotting and siRNA transfection were used to identify the effects of necroptotic human gingival fibroblasts (hGFs) on THP\u20101 macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Re\u2010analysis revealed that gingival fibroblasts (GFs) in periodontitis gingiva showed the highest area under the curve score of necroptosis. Elevated levels of necroptosis\u2010associated proteins were identified in GFs in periodontitis gingiva collected from patients and mice. In ligature\u2010induced periodontitis mice, local administration of receptor interacting protein kinase 3(RIPK3) inhibitor GSK\u2032872 or sh\u2010mixed\u2010lineage kinase domain\u2010like pseudokinase (Mlkl) markedly abrogated necroptosis and rescued periodontitis. Analogously, necroptosis inhibitors alleviated the inflammatory response and release of damage\u2010associated molecular patterns in lipopolysaccharide\u2010 or LAZ (LPS + AZD'5582 + z\u2010VAD\u2010fmk, necroptosis inducer)\u2010induced GFs and then reduced THP\u20101 cell migration and M1 polarization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Necroptosis in GFs aggravated gingival inflammation and alveolar bone loss. Necroptosis inhibitors attenuate this process by modulating THP\u20101 macrophage migration and polarization. This study offers novel insights into the pathogenesis and potential therapeutic targets of periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcpe.13841","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T11:19:35Z","timestamp":1687864775000},"page":"1264-1279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Inhibition of gingival fibroblast necroptosis mediated by RIPK3\/MLKL attenuates periodontitis"],"prefix":"10.1111","volume":"50","author":[{"given":"Kaiying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Stomatology, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Nanfang Hospital Southern Medical University  Guangzhou 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