{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:11:40Z","timestamp":1792588300222,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE027648"],"award-info":[{"award-number":["R01DE027648"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["K02DE029531"],"award-info":[{"award-number":["K02DE029531"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Fluoride is widely used in dentistry for its caries prevention. To reduce dental caries, the optimal fluoride concentration of public water supplies in the United States is 0.7\u2009ppm. However, excessive systemic fluoride consumption can lead to dental\/enamel fluorosis. Numerous studies have explored the effects of fluoride on enamel and enamel\u2010forming cells. However, research on systemic fluoride's impact on dentine is limited, particularly the effect of fluoride on the structure of the dentine\u2013pulp complex. Therefore, this study aimed to identify how excessive fluoride affects dentine microstructure using an experimental mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>C57BL6\/J male mice (6\u20139\u2009weeks old) were randomized into four groups (Fluoride at 0, 50, 100, or 125\u2009ppm in drinking water) (<jats:italic>n<\/jats:italic>\u2009=\u20094\/group). Mice were provided water ad\u00a0libitum for 6\u2009weeks along with fluoride\u2010free food. Thereafter, mandibular incisors were analysed. Enamel phenotypes were evaluated using light microscopy and quantitative light\u2010induced fluorescence (QLF) to measure fluorosis levels. Dentine morphology was evaluated using micro\u2010CT, scanning electron microscopy (SEM), SEM\u2013EDX (energy\u2010dispersive X\u2010ray), microhardness test and histological imaging. Data were analysed using one\u2010way ANOVA with Dunnett's multiple comparisons as a post hoc test and the Kruskal\u2013Wallis test with Dunn's multiple comparisons post hoc test (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mice treated with fluoride at 50\u2013125\u2009ppm developed enamel hypoplasia in their erupting incisors and micro\u2010CT imaging revealed that fluoride 125\u2009ppm caused external resorption of the growing incisor. Dentine mineral density, dentine volume decreased compared with the 0\u2009ppm control, while pulp volume increased compared with the 0\u2009ppm control group. SEM showed wider predentine layer and abnormalities in calcified matrix vesicles derived from odontoblasts in fluoride 100 and 125\u2009ppm groups. Vickers microhardness of dentine significantly decreased in the high\u2010dose group. Fluoride\u2010induced dentine hypoplasia in a dose\u2010dependent manner. Histological evaluation showed excessive fluoride 125\u2009ppm induced micro abscess formation and inflammatory cell infiltration. Fluoride induced dentine dysplasia with a dentine microstructure resembling hypophosphatasia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>High doses of systemic fluoride can cause dentine dysplasia. Both three\u2010dimensional and microstructural analyses showed the structural, chemical and mechanical changes in the dentine and the mineralized tissue components, along with external resorption and pulp inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.14150","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T16:05:36Z","timestamp":1728576336000},"page":"128-140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Ultrastructural evaluation of adverse effects on dentine formation from systemic fluoride application in an experimental mouse model"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3759-5031","authenticated-orcid":false,"given":"Motoki","family":"Okamoto","sequence":"first","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Mendonca","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Brueckner","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ria","family":"Achong\u2010Bowe","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2931-3583","authenticated-orcid":false,"given":"Nanako","family":"Kuriki","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"},{"name":"Department of Restorative Dentistry and Endodontology Osaka University Graduate School of Dentistry  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Mizuhira","sequence":"additional","affiliation":[{"name":"Bruker Japan K.K. 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