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• W2135184057 endingPage "e10895" @default.
• W2135184057 startingPage "e10895" @default.
• W2135184057 abstract "Background It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F−). Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of F−. Enamel formation is initiated in a neutral pH environment (secretory stage); however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage). Low pH can facilitate entry of F− into cells. Here, we asked if F− was more toxic at low pH, as measured by increased cell stress and decreased cell function. Methodology/Principal Findings Treatment of ameloblast-derived LS8 cells with F− at low pH reduced the threshold dose of F− required to phosphorylate stress-related proteins, PERK, eIF2α, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase, and secretion was quantified as a function of F− dose and pH. Luciferase secretion significantly decreased within 2 hr of F− treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm F− in their drinking water exhibited increased stress-mediated phosphorylation of eIF2α in maturation stage ameloblasts (pH<6.0) as compared to secretory stage ameloblasts (pH∼7.2). Intriguingly, F−-treated rats demonstrated a striking decrease in transcripts expressed during the maturation stage of enamel development (Klk4 and Amtn). In contrast, the expression of secretory stage genes, AmelX, Ambn, Enam and Mmp20, was unaffected. Conclusions The low pH environment of maturation stage ameloblasts facilitates the uptake of F−, causing increased cell stress that compromises ameloblast function, resulting in dental fluorosis." @default.
• W2135184057 created "2016-06-24" @default.
• W2135184057 creator A5006600622 @default.
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• W2135184057 creator A5072183451 @default.
• W2135184057 creator A5076385445 @default.
• W2135184057 date "2010-05-28" @default.
• W2135184057 modified "2023-09-24" @default.
• W2135184057 title "The Acid Test of Fluoride: How pH Modulates Toxicity" @default.
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• W2135184057 doi "https://doi.org/10.1371/journal.pone.0010895" @default.
• W2135184057 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2878349" @default.
• W2135184057 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20531944" @default.
• W2135184057 hasPublicationYear "2010" @default.
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