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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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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LS8 cell apoptosis induced by NaF through p-ERK and p-JNK - a mechanism study of dental fluorosis
OBJECTIVE: To investigate the possible biological mechanism of dental fluorosis at a molecular level. MATERIAL AND METHODS: Cultured LS8 were incubated with serum-free medium containing selected concentrations of NaF (0???2?mM) for either 24 or 48?h. Subcellular microanatomy was characterized using TEM; meanwhile, selected biomolecules were analysed using various biochemistry techniques. Transient
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Histone acetyltransferase promotes fluoride toxicity in LS8 cells.
Previously we demonstrated that fluoride increased acetylated-p53 (Ac-p53) in LS8 cells that are derived from mouse enamel organ epithelia and in rodent ameloblasts. However, how p53 is acetylated by fluoride and how the p53 upstream molecular pathway responds to fluoride is not well characterized. Here we demonstrate that fluoride activates
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Fluoride Alters Klk4 Expression in Maturation Ameloblasts through Androgen and Progesterone Receptor Signaling.
Fluorosed maturation stage enamel is hypomineralized in part due to a delay in the removal of matrix proteins to inhibit final crystal growth. The delay in protein removal is likely related to reduced expression of kallikrein-related peptidase 4 (KLK4), resulting in a reduced matrix proteinase activity that found in fluorosed
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Fluoride induced endoplasmic reticulum stress and calcium overload in ameloblasts
OBJECTIVE: The aim of the study was to evaluate the involvement of endoplasmic reticulum stress and intracellular calcium overload on the development of dental fluorosis. METHODS: We cultured and exposed rat ameloblast HAT-7 cells to various concentrations of fluoride and measured apoptosis with flow cytometry and intracellular Ca2+ changes using confocal
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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 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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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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Community Fluorosis Index (CFI)
The current Community Fluorosis Index for U.S. adolescents as a whole (from both fluoridated and non-fluoridated areas) is roughly 5 times higher than the CFI health authorities predicted for fluoridated areas when fluoridation first began. It is also higher than the CFI that the NIDR found in fluoridated areas back in the 1980s. It is readily apparent, therefore, that children are ingesting far more fluoride than was the case in the 1950s, and even as recently as the 1980s.
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Dental Fluorosis: The "Cosmetic" Factor
Any condition that can cause children to be embarrassed about their physical appearance can have significant consequences on their self-esteem and confidence. Researchers have repeatedly found that "physical appearance [is] the best predictor of self-esteem" in adolescents, (Harter 2000) and that facial attractiveness, particularly the appearance of one's teeth, is a
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