title: Excessive fluoride reduces Foxo1 expression in dental epithelial cells of the rat incisor.
abstract: Enamel fluorosis is characterized by hypomineralization, and forkhead box O1 (Foxo1) is essential for mouse enamel biomineralization. This study investigated the effect of fluoride on Foxo1 expression and its implications for enamel fluorosis. Mandibular incisors were extracted from Sprague Dawley rats treated for 3 months with water containing 0, 50, or 100 p.p.m. F⁻. Immunohistochemistry was used to localize and quantify FOXO1 expression in dental epithelial layer cells of the incisors. The effect of fluoride on expression of Foxo1, kallikrein-4 (Klk4), and amelotin (Amtn) mRNAs was analyzed by real-time RT-PCR, and western blotting was used to measure total and nuclear FOXO1 protein levels in mature dental epithelial cells. The results revealed that nuclear FOXO1 was mainly localized in the transition and the mature ameloblasts and exhibited weaker expression in the rats exposed to fluoride. In addition to the reduced levels of Foxo1, Klk4, and AmtnmRNAs, the protein levels of total and nuclearFOXO1 were decreased in the mature dental epithelial cells exposed to fluoride. Thus, excessive fluoride may have an effect on the expression levels of Foxo1 in dental epithelial cells and thereby affect hypomineralization of the enamel during fluorosis.
authors.affiliation: Department of Oral Prevention, School of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Gao
authors.forename: Jianping
authors.initials: J
authors.lastname: Ruan
authors.forename: Liping
authors.initials: L
authors.lastname: Gao
mesh_terms: D000565:Ameloblasts / Q000187:drug effects; D000566:Amelogenesis / Q000187:drug effects; D000818:Animals; D002327:Cariostatic Agents / Q000633:toxicity*; D002467:Cell Nucleus / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects; D003743:Dental Enamel / Q000187:drug effects; D003746:Dental Enamel Proteins / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D005459:Fluorides / Q000633:toxicity*; D009050:Fluorosis, Dental / Q000209:etiology; D051858:Forkhead Transcription Factors / Q000187:drug effects*; D007180:Incisor / Q000166:cytology* / Q000187:drug effects; D007610:Kallikreins / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071161:Forkhead Box Protein O1
chemical_list: D002327:Cariostatic Agents; D003746:Dental Enamel Proteins; D005459:Fluorides; D051858:Forkhead Transcription Factors; D007610:Kallikreins; D009419:Nerve Tissue Proteins; C514056:Amtn protein, rat; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C120801:kallikrein 4
keywords: dental epithelial cells; enamel fluorosis; forkhead box O1; hypomineralization