ArticleJournal of dental research2014
Fluoride affects enamel protein content via TGF-β1-mediated KLK4 inhibition.
Article in Journal of dental research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Prevalence and association of Molar Incisor Hypomineralization (MIH) in patients presenting dental fluorosis: a systematic review and meta-analysis.BMC oral health · 2026Pooled 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
- 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
- Proteomic Signatures of Dental Enamel Hypomineralization: Divergent Molecular Pathways in Coal-Burning vs. Drinking-Water Fluorosis.Biological trace element research · 2026Article
- Effects of fluoride and lead on enamel composition during the maturation stage of amelogenesis in rat mandibular third molars.Calcified tissue international · 2026Review
- Developmental vulnerability to fluoride toxicity: enamel and clearance differences in adolescent versus mature mice.Archives of toxicology · 2026Article
- The role of the TGF-β1 signaling pathway in the process of amelogenesis.Frontiers in physiology · 2025Review
- Hypoxic Regulation of the KLK4 Gene in two Different Prostate Cancer Cells Treated with TGF- β.Cell biochemistry and biophysics · 2024Article
- ERS Mediated by GRP-78/PERK/CHOP Signaling Is Involved in Fluoride-Induced Ameloblast Apoptosis.Biological trace element research · 2024Article
- TGF-β1/Smad3 Signaling Is Required to Alleviate Fluoride-Induced Enamel Hypomineralization.Biological trace element research · 2024Article
- Effect of Long Non-coding RNA and DNA Methylation on Gene Expression in Dental Fluorosis.Biological trace element research · 2024Article
- Perfluorooctanoic acid-induced cell death via the dual roles of ROS-MAPK/ERK signaling in ameloblast-lineage cells.Ecotoxicology and environmental safety · 2023Article
- Fluoride in the Central Nervous System and Its Potential Influence on the Development and Invasiveness of Brain Tumours-A Research Hypothesis.International journal of molecular sciences · 2023Review
- Fluoride Alters Signaling Pathways Associated with the Initiation of Dentin Mineralization in Enamel Fluorosis Susceptible Mice.Biological trace element research · 2021Article
- 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
- Sirt1 overexpression suppresses fluoride-induced p53 acetylation to alleviate fluoride toxicity in ameloblasts responsible for enamel formation.Archives of toxicology · 2018Article
- DENTAL ENAMEL FORMATION AND IMPLICATIONS FOR ORAL HEALTH AND DISEASE.Physiological reviews · 2017Review
- Fluoride Regulate Osteoblastic Transforming Growth Factor-β1 Signaling by Mediating Recycling of the Type I Receptor ALK5.PloS one · 2017Article
- No Change in Bicarbonate Transport but Tight-Junction Formation Is Delayed by Fluoride in a Novel Ameloblast Model.Frontiers in physiology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Dental fluorosis is caused by chronic high-level fluoride (F(-)) exposure during enamel development, and fluorosed enamel has a higher than normal protein content. Matrix metalloproteinase 20 cleaves enamel matrix proteins during the secretory stage, and KLK4 further cleaves these proteins during the maturation stage so that the proteins can be reabsorbed from the hardening enamel. We show that transforming growth factor β1 (TGF-β1) can induce Klk4 expression, and we examine the effect of F(-) on TGF-β1 and KLK4 expression. We found that in vivo F(-) inhibits Klk4 but not Mmp20 transcript levels. LacZ-C57BL/6-Klk4 (+/LacZ) mice have LacZ inserted in frame at the Klk4 translation initiation site so that the endogenous Klk4 promoter drives LacZ expression in the same temporal/spatial way as it does for Klk4. KLK4 protein levels in rat enamel and β-galactosidase staining in LacZ-C57BL/6-Klk4 (+/LacZ) mouse enamel were both significantly reduced by F(-) treatment. Since TGF-β1 induces KLK4 expression, we tested and found that F(-) significantly reduced Tgf-β1 transcript levels in rat enamel organ. These data suggest that F(-)-mediated downregulation of TGF-β1 expression contributes to reduced KLK4 protein levels in fluorosed enamel and provides an explanation for why fluorosed enamel has a higher than normal protein content.
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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.