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 ?1 (TGF-?1) can induce Klk4 expression, and we examine the effect of F– on TGF-?1 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 ?-galactosidase staining in LacZ-C57BL/6-Klk4 +/-LacZ mouse enamel were both significantly reduced by F– treatment. Since TGF-?1 induces KLK4 expression, we tested and found that F– significantly reduced Tgf-?1 transcript levels in rat enamel organ. These data suggest that F–-mediated downregulation of TGF-?1 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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High-fluoride promoted phagocytosis-induced apoptosis in a matured ameloblast-like cell line
Endocytosis and phagocytosis are important physiologic activities occurring during ameloblast differentiation. We have previously found that excess fluoride inhibited ameloblasts endocytotic functions. Here, we hypothesized that increasing amounts of fluoride may affect ameloblast phagocytotic function during their differentiation. Using cell culture, we first induced maturation of the mouse ameloblast-like LS8
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Fluorosed mouse ameloblasts have increased SATB1 retention and Gaq activity
Dental fluorosis is characterized by subsurface hypomineralization and increased porosity of enamel, associated with a delay in the removal of enamel matrix proteins. To investigate the effects of fluoride on ameloblasts, A/J mice were given 50 ppm sodium fluoride in drinking water for four weeks, resulting serum fluoride levels of
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Effects of Fluoride on Oxidative Stress Markers of Lipid, Gene, and Protein in Rats.
Endemic fluorosis is a systemic chronic disease caused by excessive intake of fluoride. It is widely accepted that oxidative stress is closely related to fluorosis; however, molecular mechanism of oxidative stress in fluorosis remains unclear. This study investigated the effects of fluoride (F) on oxidative stress markers of lipid, gene,
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Effect of fluoride ions on apatite crystal formation in rat hard tissues.
Fluoride is widely believed to be a useful chemical substance for preventing dental caries. However, the mechanism underlying crystal perforation in the tooth enamel and the effect of fluoride on hard tissues are unclear. To clarify the mechanism of the biological action of fluoride in the mineralization process, we examined
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Sirtuin1 and autophagy protect cells from fluoride-induced cell stress
Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase functioning in the regulation of metabolism, cell survival and organismal lifespan. Active SIRT1 regulates autophagy during cell stress, including calorie restriction, endoplasmic reticulum (ER) stress and oxidative stress. Previously, we reported that fluoride induces ER-stress in ameloblasts responsible for enamel formation,
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Dental Fluorosis Is a "Hypo-mineralization" of Enamel
Teeth with fluorosis have an increase in porosity in the subsurface enamel ("hypomineralization"). The increased porosity of enamel found in fluorosis is a result of a fluoride-induced impairment in the clearance of proteins (amelogenins) from the developing teeth. Despite over 50 years of research, the exact mechanism by which fluoride impairs amelogin
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Mechanisms by Which Fluoride Causes Dental Fluorosis Remain Unknown
When it comes to how fluoride impacts human health, no tissue in the body has been studied more than the teeth. Yet, despite over 50 years of research, the mechanism by which fluoride causes dental fluorosis (a hypo-mineralization of the enamel that results in significant staining of the teeth) is not
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Dental Fluorosis in the U.S. 1950-2004
Before the widespread use of fluoride in dentistry, dental fluorosis was rarely found in western countries. Today, with virtually every toothpaste now containing fluoride, and most U.S. water supplies containing fluoride chemicals, dental fluorosis rates have reached unprecedented levels. In the 1950s, it was estimated that only 10% of children in
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Diagnostic Criteria for Dental Fluorosis: The TSIF ("Total Surface Index of Fluorosis")
The traditional criteria (the "Dean Index") for diagnosing dental fluorosis was developed in the first half of the 20th century by H. Trendley Dean. While the Dean Index is still widely used in surveys of fluorosis -- including the CDC's national surveys of fluorosis in the United States -- dental
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"Mild" Dental Fluorosis: Perceptions & Psychological Impact
The vast majority of research has found that patients, parents, and the general public alike view mild fluorosis (TF score 3) as a significant blemish of the teeth, one that is likely to embarrass the affected child to a degree that cosmetic treatment would be warranted.
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