Fluoride ions are highly reactive, and their incorporation in forming dental enamel at low concentrations promotes mineralization. In contrast, excessive fluoride intake causes dental fluorosis, visually recognizable enamel defects that can increase the risk of caries. To investigate the molecular bases of dental fluorosis, we analyzed the effects of fluoride exposure in enamel cells to assess its impact on Ca2+ signaling. Primary enamel cells and an enamel cell line (LS8) exposed to fluoride showed decreased internal Ca2+ stores and store-operated Ca2+ entry (SOCE). RNA-sequencing analysis revealed changes in gene expression suggestive of endoplasmic reticulum (ER) stress in fluoride-treated LS8 cells. Fluoride exposure did not alter Ca2+ homeostasis or increase the expression of ER stress-associated genes in HEK-293 cells. In enamel cells, fluoride exposure affected the functioning of the ER-localized Ca2+ channel IP3R and the activity of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) pump during Ca2+ refilling of the ER. Fluoride negatively affected mitochondrial respiration, elicited mitochondrial membrane depolarization, and disrupted mitochondrial morphology. Together, these data provide a potential mechanism underlying dental fluorosis.

中文翻译：

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氟化物暴露会改变釉质细胞中的Ca2 +信号传导和线粒体功能。

氟离子具有高反应性，它们以低浓度掺入形成牙釉质的过程中会促进矿化作用。相反，过量摄入氟化物会导致牙齿氟中毒，这是视觉上可识别的牙釉质缺陷，可增加龋齿的风险。为了调查氟牙症的分子基础，我们分析了牙釉质细胞中氟化物暴露的影响，以评估其对Ca2 +信号传导的影响。暴露于氟化物的初级搪瓷细胞和搪瓷细胞系（LS8）显示出内部Ca2 +储存减少和储存操作的Ca2 +进入（SOCE）。RNA测序分析揭示了氟化物处理的LS8细胞中内质网（ER）应激的基因表达变化。暴露于氟化物不会改变HEK-293细胞中的Ca2 +稳态或增加ER应激相关基因的表达。在釉质细胞中 氟化物暴露影响ER的Ca2 +补充过程中ER定位的Ca2 +通道IP3R的功能以及肌内质网Ca2 + -ATPase（SERCA）泵的活性。氟化物对线粒体呼吸作用产生负面影响，引起线粒体膜去极化，并破坏线粒体形态。这些数据加在一起提供了氟牙症的潜在潜在机制。