{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T07:12:52Z","timestamp":1777878772861,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) plays a central role in the molecular pathogenesis of periodontal disease. However, the epigenetic regulation attributable to microbial and inflammatory signals at the biofilm\u2013gingival interface are poorly understood. In this study, the DNA methylation alteration within the <jats:italic>TNFA<\/jats:italic> promoter in human gingival biopsies from different stages of periodontal disease is investigated and the regulatory mechanism of <jats:italic>TNFA<\/jats:italic> transcription by DNA methylation is explored.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Gingival biopsies were obtained from 17 patients with chronic periodontitis (CP) and 18 periodontally healthy individuals. Another 11 individuals participated in an experimentally induced gingivitis study, and gingival biopsies were collected at the baseline, induction, and resolution phase. To confirm that <jats:italic>TNFA<\/jats:italic> promoter methylation modulated <jats:italic>TNFA<\/jats:italic> transcription, THP.1 cells were treated with a DNA methyltransferase inhibitor, 5\u2010Aza\u20102\u2010deoxycytidine (5\u2010Aza\u20102dC), and an RAW294.7 cell line transfected with a <jats:italic>TNFA<\/jats:italic> promoter\u2010specific luciferase reporter system with or without methylation was used.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In gingival biopsies from individuals with severe CP, two individual cytosine\u2010guanine dinucleotides (CpG sites) within the <jats:italic>TNFA<\/jats:italic> promoter (at \u2212163 and \u2212161 bp) displayed increased methylation in CP samples compared to those with gingival health (16.1% \u00b1 5.1% versus 11.0% \u00b1 4.6%, <jats:italic>P<\/jats:italic> = 0.02 and 19.8% \u00b1 4.1% versus 15.4% \u00b1 3.6%, <jats:italic>P<\/jats:italic> = 0.04, respectively). The methylation level at \u2212163 bp was inversely associated with the transcription level of <jats:italic>TNFA<\/jats:italic> (<jats:italic>P<\/jats:italic> = 0.018). However, no significant difference in the <jats:italic>TNFA<\/jats:italic> promoter methylation pattern was observed in samples biopsied during the induction or resolution phase of experimentally induced gingivitis, which represented a reversible periodontal lesion. THP.1 cells treated with 5\u2010Aza\u20102dC demonstrated a time\u2010dependent increase in <jats:italic>TNFA<\/jats:italic> messenger level. It was also found that the luciferase activity decreased 2.6\u2010fold in a construct containing an in vitro methylated <jats:italic>TNFA<\/jats:italic> promoter when compared to the unmethylated insert (<jats:italic>P<\/jats:italic> = 0.03).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Although the biopsy samples represented a mixed cell population, the change in promoter methylation status in chronic periodontal disease suggested that DNA methylation may be an important regulatory mechanism in controlling <jats:italic>TNFA<\/jats:italic> transcriptional expression in periodontal disease.<\/jats:p>","DOI":"10.1902\/jop.2013.120294","type":"journal-article","created":{"date-parts":[[2013,1,31]],"date-time":"2013-01-31T10:08:52Z","timestamp":1359626932000},"page":"1606-1616","source":"Crossref","is-referenced-by-count":87,"title":["Epigenetic Regulation of <i>TNFA<\/i> Expression in Periodontal Disease"],"prefix":"10.1002","volume":"84","author":[{"given":"Shaoping","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvana P.","family":"Barros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio J.","family":"Moretti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John S.","family":"Preisser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai D.","family":"Niculescu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Offenbacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2008.080220"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2008.080183"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510376402"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2003.74.3.391"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2010.090732"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1998.tb02313.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2007.060465"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2010.01543.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2006.00908.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(90)90205-O"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81532-9"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4934fje"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-140145"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034509356512"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910708600212"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1965.36.3.177"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.13.e65"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2010.01616.x"},{"key":"e_1_2_7_20_1","first-page":"251","article-title":"In 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