ArticlePloS one2010
The acid test of fluoride: how pH modulates toxicity.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- Morphological, Histochemical, and Proteomic Analysis of the Effects of Fluoride and Amoxicillin, with Calcium and Vitamin D Supplementation, on Dental Enamel Formation.Calcified tissue international · 2026Article
- Benchmark Approach to Unravel Fluoride Toxicity: Liver and Kidney Disruptions in Subacutely Exposed Rats.Journal of xenobiotics · 2026Article
- Dental fluorosis in the European roe deer (Capreolus capreolus): A review of the pathological changes in the enamel of fluorotic cheek teeth and the abnormal pattern of dental wear in affected dentitions.Anatomical record (Hoboken, N.J. : 2007) · 2026Review
- Fluoride Alters Gene Expression via Histone H3K27 Acetylation in Ameloblast-like LS8 Cells.International journal of molecular sciences · 2024Article
- Article
- ERS Mediated by GRP-78/PERK/CHOP Signaling Is Involved in Fluoride-Induced Ameloblast Apoptosis.Biological trace element research · 2024Article
- Biphasic Functions of Sodium Fluoride (NaF) in Soft and in Hard Periodontal Tissues.International journal of molecular sciences · 2022Review
- Exogenous transforming growth factor-β1 prevents the inflow of fluoride to ameleoblasts through regulation of voltage-gated chloride channels 5 and 7.Experimental and therapeutic medicine · 2021Article
- Curcumin suppresses cell growth and attenuates fluoride-mediated Caspase-3 activation in ameloblast-like LS8 cells.Environmental pollution (Barking, Essex : 1987) · 2021Article
- Serum Concentration of Fluoride in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland.International journal of environmental research and public health · 2021Article
- Does fluoride cause the mysterious chronic kidney disease of multifactorial origin?Environmental geochemistry and health · 2020Review
- Histone acetyltransferase promotes fluoride toxicity in LS8 cells.Chemosphere · 2020Article
- Article
- A mini review of fluoride-induced apoptotic pathways.Environmental science and pollution research international · 2018Review
- How pH is regulated during amelogenesis in dental fluorosis.Experimental and therapeutic medicine · 2018Review
- Article
- Meeting report: a hard look at the state of enamel research.International journal of oral science · 2017Article
- The Unfolded Protein Response in Amelogenesis and Enamel Pathologies.Frontiers in physiology · 2017Review
- 4-phenylbutyrate Mitigates Fluoride-Induced Cytotoxicity in ALC Cells.Frontiers in physiology · 2017Article
- Dopaminergic Neurons Exhibit an Age-Dependent Decline in Electrophysiological Parameters in the MitoPark Mouse Model of Parkinson's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIt 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
findingsTreatment of ameloblast-derived LS8 cells with F(-) at low pH reduced the threshold dose of F(-) required to phosphorylate stress-related proteins, PERK, eIF2alpha, 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 eIF2alpha in maturation stage ameloblasts (pH<6.0) as compared to secretory stage ameloblasts (pH approximately 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.
conclusionsThe low pH environment of maturation stage ameloblasts facilitates the uptake of F(-), causing increased cell stress that compromises ameloblast function, resulting in dental fluorosis.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.