{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:59:20Z","timestamp":1780981160865,"version":"3.54.1"},"reference-count":67,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T00:00:00Z","timestamp":1490572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006582","name":"College of Dentistry, University of Tennessee","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006582","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Vitamin D\u20141,25(<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content>)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>or 1,25D3\u2014maintains healthy osseous tissue, stimulates the production of the antimicrobial peptide cathelicidin and has anti\u2010inflammatory effects, but it can cause hypercalcemia. Evidence links diminished serum levels of 1,25D3 with increased gingival inflammation. Periodontitis progression is associated with increased local production of inflammatory mediators by immune cells and gingival fibroblasts. These include interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20106, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108, both regulated by signaling pathways, including<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">\u03baB<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101. The objectives were to determine the effects of 1,25D3 or a non\u2010calcemic analog, 20\u2010hydroxyvitamin D<jats:sub>3<\/jats:sub>\u201420(<jats:styled-content style=\"fixed-case\">OH<\/jats:styled-content>)D<jats:sub>3<\/jats:sub>or 20D3\u2014on<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2\u2010stimulated<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 production, and<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">\u03baB<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101 activation, by human gingival fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Human gingival fibroblasts were incubated \u00b1<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2, with or without exposure to 1,25D3 or 20D3.<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 in culture supernatants were measured by enzyme\u2010linked immunosorbent assay.<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB (p65) and<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101 (phospho\u2010<jats:styled-content style=\"fixed-case\">cJ<\/jats:styled-content>un) and were measured in nuclear extracts via binding to specific oligonucleotides. Data were analyzed using<jats:styled-content style=\"fixed-case\">ANOVA<\/jats:styled-content>and Scheffe's F procedure for post hoc comparisons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2\u2010stimulated<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 levels were both significantly inhibited (40%\u201060%) (<jats:italic>P<\/jats:italic>&lt;.045) by 1,25D3, but not 20D3 (0%\u201015% inhibition, not statistically significant). Both 1,25D3 and 20D3 significantly and similarly inhibited<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2\u2010stimulated nuclear levels of p65 and phospho\u2010<jats:styled-content style=\"fixed-case\">cJ<\/jats:styled-content>un (<jats:italic>P<\/jats:italic>&lt;.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Reduction of the activation of<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB and<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101 alone is not able to inhibit strongly the<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 stimulated<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 gene expression. 1,25D3 but not 20D3 may affect some of the many other factors\/processes\/pathways that in turn regulate the expression of these genes. However, the results suggest that topical application of ligands of the vitamin D receptor may be useful in the local treatment of periodontitis while reducing adverse systemic effects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12452","type":"journal-article","created":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T10:24:56Z","timestamp":1490610296000},"page":"832-841","source":"Crossref","is-referenced-by-count":26,"title":["Effect of 1,25(<scp>OH<\/scp>)<sub>2<\/sub>D<sub>3<\/sub>and 20(<scp>OH<\/scp>)D<sub>3<\/sub>on interleukin\u20101\u03b2\u2010stimulated interleukin\u20106 and \u20108 production by human gingival fibroblasts"],"prefix":"10.1111","volume":"52","author":[{"given":"V.","family":"Nakashyan","sequence":"first","affiliation":[{"name":"College of Dentistry Department of Periodontology University of Tennessee Health Science Center Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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