{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:21:49Z","timestamp":1789381309890,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The aim of this study was to investigate the effect of type 2 diabetes (T2D) on clinically normal dental pulp tissue by using special stains and immunohistochemistry (IHC) to determine the morphology of the coronal pulp and distribution of immune markers in non\u2010T2D and T2D groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      Ethics approval for this\n                      <jats:italic>in vitro<\/jats:italic>\n                      pilot study was obtained from the University of Otago Human Ethics Committee (16\/069). Twenty extracted permanent molar teeth diagnosed as having clinically normal pulp status were collected. Ten teeth were from participants with well\u2010controlled T2D and ten from participants without diabetes (non\u2010T2D). Each tooth was sectioned transversely at the cemento\u2010enamel junction before the crowns were decalcified and embedded in paraffin. Sections were stained with haematoxylin and eosin, Massons trichrome, and van Gieson stains for histological and morphological evaluation. IHC using anti\u2010CD4, anti\u2010CD68 and anti\u2010CD83 and anti\u2010IL1\u03b2, anti\u2010IL6, anti\u2010IL17, anti\u2010TNF\u2010\u03b1, anti\u2010TLR2, anti\u2010TLR4 and anti\u2010FOXP3 identified proteins of interest. Qualitative and semi\u2010quantitative analyses evaluated the morphology of the dental pulp and protein expression. Data analyses were performed with GraphPad Prism, using Student's\n                      <jats:italic>t<\/jats:italic>\n                      \u2010test and multiple regression using SPSS at\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.05.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Special stains demonstrated morphological differences in the T2D dental pulp compared with non\u2010T2D. Qualitative analysis indicated that the pulp in the T2D samples was consistently less cellular, less vascular, showed evidence of thickened blood vessel walls, increased pulp calcification and collagen deposition. Semi\u2010quantitative analysis of IHC samples showed the T2D pulp had significantly increased expression of macrophage and dendritic cell markers CD68 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.001) and CD83 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.04), and there was significantly greater expression of inflammatory cytokines IL1\u03b2 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.01), IL6 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.0001), IL17 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.0001) and TNF\u2010\u03b1 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.01). T2D samples showed a significant increase in markers of innate inflammation, TLR2 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.001) and TLR4 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.001) and decreased expression of regulatory T\u2010cell marker, FOXP3 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.01). Multiple regression showed that age\u2010corrected differences were statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Preliminary findings suggest that T2D may exert a similar response in the pulp to complications in other body sites. Hyperglycaemia is associated with changes in the morphology of the clinically normal dental pulp with altered immune cell and cytokine expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.13732","type":"journal-article","created":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T17:49:58Z","timestamp":1648144198000},"page":"660-671","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Type 2 diabetes and the clinically normal pulp: An\n                    <i>in vitro<\/i>\n                    study"],"prefix":"10.1111","volume":"55","author":[{"given":"Shaikhah","family":"Alsamahi","sequence":"first","affiliation":[{"name":"Sir John Walsh Research Institute Faculty of Dentistry University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trudy M.","family":"Milne","sequence":"additional","affiliation":[{"name":"Sir John Walsh Research Institute 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