{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T03:46:26Z","timestamp":1762659986698,"version":"3.37.3"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:00:00Z","timestamp":1599004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Periodontitis is a chronic inflammatory disease that results in the destruction of periodontal soft tissue and the resorption of alveolar bone. Evidence indicates that in diabetic patients, hyperglycemia suppresses periodontal ligament stem cell (PDLSC) functions and leads to difficulties in periodontal repair. The present study aimed to explore the mechanisms by which high\u2010glucose concentrations aggravate cell viability reduction in human CD146\u2010positive PDLCs (CD146<jats:sup>+<\/jats:sup>PDLCs) under tumor necrosis factor\u2010alpha (TNF\u2010alpha) induction. CD146<jats:sup>+<\/jats:sup>PDLCs were isolated from periodontal ligament tissues and treated in the absence or presence of 10\u2009ng\/ml of TNF\u2010alpha and 30\u2009mM glucose. Cell viability was detected using Cell Counting Kit\u20108 assays and Luminescent Cell Viability Assays. Western blotting and real\u2010time polymerase chain reaction were performed to determine tumor necrosis factor\u2010alpha receptor\u20101 (TNFR\u20101) protein and messenger RNA expression. Bisulfite and MassArray methylation analyses were used to analyze the methylation status of the TNFR\u20101 gene. Our results indicated that cell viability was reduced after treatment with a combination of both high\u2010glucose concentration and TNF\u2010alpha. Treatment with 30\u2009mM glucose suppressed DNA methyltransferase (DNMT) activities and DNMT1 protein expression, and this was accompanied by the upregulation of TNFR\u20101. Additionally, we found that the CpG island located within the TNFR\u20101 gene was hypomethylated under 30\u2009mM glucose conditions. <jats:italic>S<\/jats:italic>\u2010adenosylmethionine, an established methyl donor, reversed TNFR\u20101 upregulation and restored cell viability against high\u2010glucose concentration and TNF\u2010alpha. In conclusion, the present findings suggest that high\u2010glucose\u2010induced CpG island hypomethylation within the TNFR\u20101 gene plays an essential role in TNFR\u20101 upregulation, and this further enhances the cell viability reduction of CD146<jats:sup>+<\/jats:sup>PDLCs caused by TNF\u2010alpha.<\/jats:p>","DOI":"10.1002\/cbin.11445","type":"journal-article","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T19:29:33Z","timestamp":1598556573000},"page":"2383-2394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["High\u2010glucose concentration aggravates TNF\u2010alpha\u2010induced cell viability reduction in human CD146\u2010positive periodontal ligament cells via TNFR\u20101 gene demethylation"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6084-8503","authenticated-orcid":false,"given":"Haoyuan","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Periodontology, Guanghua School of Stomatology, Hospital of Stomatology Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Guanghua School of Stomatology, Hospital of Stomatology Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyan","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Guanghua School of Stomatology, Hospital of Stomatology Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Guanghua School of Stomatology, Hospital of Stomatology Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-S002"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12549"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2007.01127.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.947102"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.02.006"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2012.04.003"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211813200"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706979"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2012.01500.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100459"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2009.01593.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03260.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345010800100301"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2011.03.015"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2012.120547"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/137.2.339"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3230"},{"issue":"151","key":"e_1_2_10_19_1","first-page":"1418","article-title":"TNF\u2010alpha mediated apoptosis plays an important role in the development of early diabetic retinopathy and long\u2010term histopathological alterations","volume":"15","author":"Joussen A. 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