{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:23:17Z","timestamp":1791904997627,"version":"4.3.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T00:00:00Z","timestamp":1518480000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE021921, R01DE017732"],"award-info":[{"award-number":["R01DE021921, R01DE017732"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>Diabetes mellitus increases periodontitis and pathogenicity of the oral microbiome. To further understand mechanisms through which diabetes affects periodontitis, we examined its impact on periodontal ligament fibroblasts in vivo and in vitro. Periodontitis was induced by inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in normoglycemic and diabetic mice. Diabetes, induced by multiple low-dose injections of streptozotocin increased osteoclast numbers and recruitment of neutrophils to the periodontal ligament, which could be accounted for by increased CXC motif chemokine 2 (CXCL2) and receptor activator of nuclear factor kappa B ligand (RANKL) expression by these cells. Diabetes also stimulated a significant increase in nuclear factor kappa B (NF-\u03baB) expression and activation in periodontal ligament (PDL) fibroblasts. Surprisingly, we found that PDL fibroblasts express a 2.3-kb regulatory unit of Col1\u03b11 (collagen type 1, alpha 1) promoter typical of osteoblasts. Diabetes-enhanced CXCL2 and RANKL expression in PDL fibroblasts was rescued in transgenic mice with lineage-specific NF-\u03baB inhibition controlled by this regulatory element. In vitro, high glucose increased NF-\u03baB transcriptional activity, NF-\u03baB nuclear localization, and RANKL expression in PDL fibroblasts, which was reduced by NF-\u03baB inhibition. Thus, diabetes induces changes in PDL fibroblast gene expression that can enhance neutrophil recruitment and bone resorption, which may be explained by high glucose\u2013induced NF-\u03baB activation. Furthermore, PDL fibroblasts express a regulatory element in vivo that is typical of committed osteoblasts.<\/jats:p>","DOI":"10.1177\/0022034518755697","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T21:05:03Z","timestamp":1518555903000},"page":"580-588","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":67,"title":["Diabetes Activates Periodontal Ligament Fibroblasts via NF-\u03baB In Vivo"],"prefix":"10.1177","volume":"97","author":[{"given":"J.","family":"Zheng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"},{"name":"Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 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