Abstract
Fluorine is a bone‐seeking element ubiquitously present in the environment and widely used in many oral hygiene products. In humans, excessive intake of fluoride may cause dental and skeletal fluorosis. However, endemic fluorosis does not appear to develop in a proportion of individuals exposed to the same levels of fluoride. The mechanisms by which mammalian cells resist fluoride are still unclear. In this study, we developed strains of mouse L‐929 cells resistant to different levels of fluoride. High‐throughput RNA‐sequencing analyses of the fluoride‐resistant L‐929 cells indicated that massive changes in global gene expression occurred, compared with the wild‐type L‐929 cells. The main biological processes and functions changed were associated with the extracellular region and matrix, response to stress, receptor binding, and signal transduction. This indicated that high doses of fluoride not only exerted stress on L‐929 cells but also induced functional pathways that helped them adapt to the presence of fluoride or to expel it. These data should prove useful in identifying cellular processes or transporters/channels that play central roles in adaptation to or expulsion of fluoride in humans.
Highlights
Fluorine is a bone-seeking element ubiquitously present in the environment and widely used in many oral hygiene products
Excessive intake of fluoride may cause dental and skeletal fluorosis, two most common endemic fluorosis associated with excessive fluoride exposure
Dental fluorosis leads to pitting, perforation, and chipping of the teeth, whereas skeletal fluorosis causes more severe consequences like pains in joints followed by stiffness, which leads to Abbreviations ECM, extracellular matrix; FoxO, forkhead box O; FR, fluoride-resistant; KEGG, Kyoto encyclopedia of genes and genomes; mitogen-activated protein kinase (MAPK), mitogenactivated protein kinase; MTT, methyl thiazolyl tetrazolium; NF-kappa B, nuclear factor kappa B; OD, optical densities; PI3K, phosphoinositide 3-kinase; WT, wild-type
Summary
Fluorine is a bone-seeking element ubiquitously present in the environment and widely used in many oral hygiene products. The main biological processes and functions changed were associated with the extracellular region and matrix, response to stress, receptor binding, and signal transduction This indicated that high doses of fluoride exerted stress on L-929 cells and induced functional pathways that helped them adapt to the presence of fluoride or to expel it. Dental fluorosis leads to pitting, perforation, and chipping of the teeth, whereas skeletal fluorosis causes more severe consequences like pains in joints followed by stiffness, which leads to Abbreviations ECM, extracellular matrix; FoxO, forkhead box O; FR, fluoride-resistant; KEGG, Kyoto encyclopedia of genes and genomes; MAPK, mitogenactivated protein kinase; MTT, methyl thiazolyl tetrazolium; NF-kappa B, nuclear factor kappa B; OD, optical densities; PI3K, phosphoinositide 3-kinase; WT, wild-type. Endemic fluorosis does not appear to develop in a proportion of individuals exposed to the same levels of fluoride, which suggests that some individuals are less sensitive to and/or have gained a capability to resist fluoride toxicity [9]
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