{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:51:59Z","timestamp":1787863919376,"version":"build-2784847793"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical &amp;amp; Exp Dental Res"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Epigenetic modifications such as DNA methylation play a crucial role in the regulation of gene expression in inflammatory diseases, including periodontitis. While previous studies have examined methylation changes during active disease or shortly after treatment, little is known about the epigenetic landscape of periodontal tissues that have remained clinically stable over the long term after Supportive Periodontal Therapy (SPT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected gingival tissue samples from 40 individuals, including 20 with a history of periodontitis currently under long\u2010term SPT and 20 periodontally healthy controls. DNA methylation levels of LINE\u20101 (a marker of global methylation) and inflammation\u2010related genes <jats:italic>COX\u20102<\/jats:italic> (<jats:italic>PTGS2<\/jats:italic>), <jats:italic>IFN\u2010\u03b3<\/jats:italic> (<jats:italic>IFNG<\/jats:italic>), and <jats:italic>TNF\u2010\u03b1<\/jats:italic> (<jats:italic>TNF<\/jats:italic>) were analyzed using bisulfite pyrosequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The LINE\u20101 methylation percentage was significantly higher in the periodontitis group than in the healthy group (66.5%\u2009\u00b1\u20092.0 vs. 63.9%\u2009\u00b1\u20094.0; <jats:italic>p<\/jats:italic>\u2009=\u20090.03). However, this significance was lost after adjusting for age and gender. No significant differences were observed between groups for <jats:italic>COX\u20102<\/jats:italic>, <jats:italic>IFN\u2010\u03b3<\/jats:italic>, or <jats:italic>TNF\u2010\u03b1<\/jats:italic>. Genomic context analysis using the Encyclopedia of DNA Elements annotations revealed that the CpG sites analyzed for <jats:italic>PTGS2<\/jats:italic>, <jats:italic>IFNG<\/jats:italic>, and <jats:italic>TNF<\/jats:italic> are in distal regulatory regions enriched with enhancer\u2010like elements, histone modifications, and predicted <jats:italic>NFKB1<\/jats:italic> binding motifs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that LINE\u20101 methylation in clinically stable gingival tissues may reflect long\u2010term epigenetic memory from previous chronic inflammation. Motif\u2010level analysis highlighted potential regulatory input from <jats:italic>NFKB1<\/jats:italic> at the three loci (<jats:italic>PTGS2<\/jats:italic>, <jats:italic>IFNG<\/jats:italic>, and <jats:italic>TNF<\/jats:italic>). Notably, no significant epigenetic differences were observed in the inflammation\u2010related genes <jats:italic>COX\u20102<\/jats:italic>, <jats:italic>IFN\u2010\u03b3<\/jats:italic>, and <jats:italic>TNF\u2010\u03b1<\/jats:italic>, suggesting that periodontal disease can be effectively treated and that certain inflammatory markers may return to levels comparable to those seen in individuals who have never had the disease. These results highlight the importance of examining DNA methylation dynamics not only during active disease but also during long\u2010term remission.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cre2.70229","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T22:34:02Z","timestamp":1759876442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["DNA Methylation of <i>COX\u20102<\/i>, <i>IFN\u2010\u03b3<\/i>, <i>TNF\u2010\u03b1<\/i>, and LINE\u20101 in Clinically Stable Periodontal Tissues Following Periodontal Therapy"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3836-147X","authenticated-orcid":false,"given":"Giulio","family":"Rasperini","sequence":"first","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences University of Milan Milan Italy"},{"name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan 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