ArticleThe Journal of biological chemistry2005
Fluoride induces endoplasmic reticulum stress in ameloblasts responsible for dental enamel formation.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 3 of them syntheses that pooled it.
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Who cites it
72 citing papers in PubMed, 3 syntheses or guidelines pooled it, 171 citations in OpenAlex.
- A Systematic Review on the Association Between Water Fluoride Levels and Dental Fluorosis: Exploring the 'Halo Effect' and Confounding Environmental Factors.International journal of molecular sciences · 2026Pooled it
- Topical fluoride as a cause of dental fluorosis in children.The Cochrane database of systematic reviews · 2024Pooled it
- Topical fluoride as a cause of dental fluorosis in children.The Cochrane database of systematic reviews · 2010Pooled it
- Quantification of Fluoride in Serum, Bone, and Teeth in a Murine Model Using Hexamethyldisiloxane-Facilitated Diffusion and Ion-Selective Electrode Measurements.Journal of visualized experiments : JoVE · 2026Article
- Effect of deep margin elevation with different base materials on periodontal health in a clinical study.Scientific reports · 2026Article
- The Cariostatic Mechanisms of Fluoride-An Updated Review.Dentistry journal · 2026Review
- Developmental vulnerability to fluoride toxicity: enamel and clearance differences in adolescent versus mature mice.Archives of toxicology · 2026Article
- Review
- Fluoride-induced Neurodevelopmental Toxicity- AMPK as a Possible Target.CNS & neurological disorders drug targets · 2025Review
- ERS Mediated by GRP-78/PERK/CHOP Signaling Is Involved in Fluoride-Induced Ameloblast Apoptosis.Biological trace element research · 2024Article
- Fluoride-Induced Mitochondrial Dysfunction and Approaches for Its Intervention.Biological trace element research · 2024Review
- Article
- Molecular basis of fluoride toxicities: Beyond benefits and implications in human disorders.Genes & diseases · 2023Review
- Review
- Unraveling molecular characteristic of fluoride neurotoxicity on U87 glial-like cells: insights from transcriptomic and proteomic approach.Frontiers in cellular neuroscience · 2023Article
- Effect of Fluoride on Cytotoxicity Involved in Mitochondrial Dysfunction: A Review of Mechanism.Frontiers in veterinary science · 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
- The Effect of Lycopene on DNA Damage and Repair in Fluoride-Treated NRK-52E Cell Line.Biological trace element research · 2021Article
- Three-Dimensional Culture of Ameloblast-Originated HAT-7 Cells for Functional Modeling of Defective Tooth Enamel Formation.Frontiers in pharmacology · 2021Article
- Estimating the Effects of Dental Caries and Its Restorative Treatment on Periodontal Inflammatory and Oxidative Status: A Short Controlled Longitudinal Study.Frontiers in immunology · 2021Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The mechanism of how fluoride causes fluorosis remains unknown. Exposure to fluoride can inhibit protein synthesis, and this may also occur by agents that cause endoplasmic reticulum (ER) stress. When translated proteins fail to fold properly or become misfolded, ER stress response genes are induced that together comprise the unfolded protein response. Because ameloblasts are responsible for dental enamel formation, we used an ameloblast-derived cell line (LS8) to characterize specific responses to fluoride treatment. LS8 cells were growth-inhibited by as little as 1.9-3.8 ppm fluoride, whereas higher doses induced ER stress and caspase-mediated DNA fragmentation. Growth arrest and DNA damage-inducible proteins (GADD153/CHOP, GADD45alpha), binding protein (BiP/glucose-responsive protein 78 (GRP78), the non-secreted form of carbonic anhydrase VI (CA-VI), and active X-box-binding protein-1 (Xbp-1) were all induced significantly after exposure to 38 ppm fluoride. Unexpectedly, DNA fragmentation increased when GADD153 expression was inhibited by short interfering RNA treatment but remained unaffected by transient GADD153 overexpression. Analysis of control and GADD153(-/-) embryonic fibroblasts demonstrated that caspase-3 mediated the increased DNA fragmentation observed in the GADD153 null cells. We also demonstrate that mouse incisor ameloblasts are sensitive to the toxic effects of high dose fluoride in drinking water. Activated Ire1 initiates an ER stress response pathway, and mouse ameloblasts were shown to express activated Ire1. Ire1 levels appeared induced by fluoride treatment, indicating that ER stress may play a role in dental fluorosis. Low dose fluoride, such as that present in fluoridated drinking water, did not induce ER stress.
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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.