Okamoto Motoki, Yamashita Shohei, Mendonca Melanie, Brueckner Susanne, Achong-Bowe Ria, Thompson Jeffrey, Kuriki Nanako, Mizuhira Manabu, Benjamin Yehuda, Duncan Henry Fergus, Everett Eric T, Suzuki Maiko
Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Florida, USA.
Department of Restorative Dentistry and Endodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
Int Endod J. 2025 Jan;58(1):128-140. doi: 10.1111/iej.14150. Epub 2024 Oct 10.
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 ppm. However, excessive systemic fluoride consumption can lead to dental/enamel fluorosis. Numerous studies have explored the effects of fluoride on enamel and enamel-forming cells. However, research on systemic fluoride's impact on dentine is limited, particularly the effect of fluoride on the structure of the dentine-pulp complex. Therefore, this study aimed to identify how excessive fluoride affects dentine microstructure using an experimental mouse model.
C57BL6/J male mice (6-9 weeks old) were randomized into four groups (Fluoride at 0, 50, 100, or 125 ppm in drinking water) (n = 4/group). Mice were provided water ad libitum for 6 weeks along with fluoride-free food. Thereafter, mandibular incisors were analysed. Enamel phenotypes were evaluated using light microscopy and quantitative light-induced fluorescence (QLF) to measure fluorosis levels. Dentine morphology was evaluated using micro-CT, scanning electron microscopy (SEM), SEM-EDX (energy-dispersive X-ray), microhardness test and histological imaging. Data were analysed using one-way ANOVA with Dunnett's multiple comparisons as a post hoc test and the Kruskal-Wallis test with Dunn's multiple comparisons post hoc test (p < .05).
Mice treated with fluoride at 50-125 ppm developed enamel hypoplasia in their erupting incisors and micro-CT imaging revealed that fluoride 125 ppm caused external resorption of the growing incisor. Dentine mineral density, dentine volume decreased compared with the 0 ppm control, while pulp volume increased compared with the 0 ppm control group. SEM showed wider predentine layer and abnormalities in calcified matrix vesicles derived from odontoblasts in fluoride 100 and 125 ppm groups. Vickers microhardness of dentine significantly decreased in the high-dose group. Fluoride-induced dentine hypoplasia in a dose-dependent manner. Histological evaluation showed excessive fluoride 125 ppm induced micro abscess formation and inflammatory cell infiltration. Fluoride induced dentine dysplasia with a dentine microstructure resembling hypophosphatasia.
High doses of systemic fluoride can cause dentine dysplasia. Both three-dimensional 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.
氟化物在牙科领域广泛用于预防龋齿。为减少龋齿,美国公共供水的最佳氟化物浓度为0.7 ppm。然而,过量摄入全身性氟化物会导致牙齿/牙釉质氟中毒。众多研究探讨了氟化物对牙釉质及成釉细胞的影响。然而,关于全身性氟化物对牙本质影响的研究有限,尤其是氟化物对牙髓复合体结构的影响。因此,本研究旨在使用实验小鼠模型确定过量氟化物如何影响牙本质微观结构。
将6至9周龄的C57BL6/J雄性小鼠随机分为四组(饮用水中氟化物浓度分别为0、50、100或125 ppm)(每组n = 4)。小鼠自由饮用含氟水6周,同时给予无氟食物。此后,对下颌切牙进行分析。使用光学显微镜和定量光诱导荧光(QLF)评估牙釉质表型以测量氟中毒水平。使用显微CT、扫描电子显微镜(SEM)、SEM能谱仪(EDX)、显微硬度测试和组织学成像评估牙本质形态。数据采用单因素方差分析及Dunnett多重比较作为事后检验,以及Kruskal-Wallis检验及Dunn多重比较事后检验进行分析(p < 0.05)。
饮用含50 - 125 ppm氟化物的小鼠在萌出的切牙中出现牙釉质发育不全,显微CT成像显示125 ppm氟化物导致正在生长的切牙外部吸收。与0 ppm对照组相比,牙本质矿物质密度、牙本质体积降低,而牙髓体积与0 ppm对照组相比增加。SEM显示在100和125 ppm氟化物组中前期牙本质层更宽,且成牙本质细胞来源的钙化基质小泡存在异常。高剂量组牙本质的维氏显微硬度显著降低。氟化物以剂量依赖方式诱导牙本质发育不全。组织学评估显示125 ppm过量氟化物诱导微脓肿形成和炎性细胞浸润。氟化物诱导牙本质发育异常,其牙本质微观结构类似于低磷酸酯酶症。
高剂量全身性氟化物可导致牙本质发育异常。三维及微观结构分析均显示牙本质及矿化组织成分在结构、化学和力学方面的变化,以及外部吸收和牙髓炎症。