The Role of Iron in Ameloblast Differentiation and Enamel Fluorosis

铁在成釉细胞分化和牙釉质氟中毒中的作用

• 批准号: 8635209
• 负责人: Michael Huan Le
• 金额: $ 3.99万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635209
• 关键词: Acquired Dental Fluorosis; Address; Affect; Ameloblasts; Antioxidants; Binding; Biological; Cell Survival; Cell physiology; Cells; Clinical; Color; Complex; DNA biosynthesis; Data; Defense Mechanisms; Dental; Dental Enamel; Dental caries; Dentists; Deposition; Development; Doctor of Philosophy; Elements; Enzymes; Exposure to; Ferritin; Fluorides; Foundations; Free Radical Formation; Free Radicals; Funding; Genes; Goals; Homeostasis; Hydrogen Peroxide; Immunohistochemistry; In Vitro; Incidence; Incisor; Ions; Iron; Iron-Binding Proteins; Lead; Maturation-Stage Ameloblast; Measurement; Measures; Mediating; Minerals; Mus; NF-kappa B; Oral; Oxidants; Oxidation-Reduction; Oxidative Stress; Pigments; Predisposition; Production; Proteins; Regulation; Relative (related person); Research; Rodent; Role; Science; Scientist; Small Interfering RNA; Superoxides; Testing; Tooth structure; Training; Transferrin Receptor; Up-Regulation; biological adaptation to stress; biomineralization; career; cell growth; cell growth regulation; craniofacial; drinking water; fluorosis; glutathione synthase; in vivo; metal transporting protein 1; mineralization; novel therapeutics; nuclear factor-erythroid 2; oxidative damage; oxygen transport; prevent; programs; public health relevance; response; superoxide dismutase 1; transcription factor; uptake

DESCRIPTION (provided by applicant): This F30 application is to provide support for the completion of my DDS-PhD training in the UCSF Program in Oral and Craniofacial Sciences. I have completed most of my clinical dental training and will focus primarily on my PhD research, which focuses on the role fluoride in altering iron transport in ameloblasts. Fluoride alters enamel biomineralization, and this is largely considered to occur through matrix mediated effects of fluoride. However, in the rodent incisor, retention of iron pigment in fluorosed maturation ameloblasts suggests a cellular mechanism by which fluoride alters iron transport in ameloblasts. Iron is important for cell function, but an excess of iron, which results in an increase in the labile iron pool, can cause free radical formation, with resultant oxidative stress Therefore, cellular regulation of iron is critical for cell growth and survival. In preliminary stuies, we found that along with increased iron retention in maturation ameloblasts, the iron binding protein, ferritin, is is also increased. Ferritin binds iron to in a crystalline form to protect th cell from iron related oxidative stress, and can be upregulated by nuclear factor kappa B (NF?B). The overall goal of this proposal is to investigate the cellular mechanisms by which fluoride enhances iron retention in ameloblasts, and the role of this mechanism in modulating oxidative stress in maturation stage ameloblasts. This goal will be addressed by the following two specific aims. Aim 1) to determine how fluoride alters iron uptake and storage in maturation stage ameloblasts; Aim 2) to determine how fluoride modulates the redox state of maturation stage ameloblasts. Understanding the underlying biological effects of fluoride on iron homeostasis will yield important information about the mechanisms behind dental fluorosis, which could lead to the identification of novel therapeutic practices to reduce the incidence of dental fluorosis.

描述（由申请人提供）：此 F30 申请旨在为我完成 UCSF 口腔和颅面科学项目的 DDS-PhD 培训提供支持。我已经完成了大部分临床牙科培训，并将主要专注于我的博士研究，该研究的重点是氟化物在改变成釉细胞中铁转运的作用。氟化物改变牙釉质生物矿化，这在很大程度上被认为是通过氟化物的基质介导作用发生的。然而，在啮齿动物门牙中，含氟成熟成釉细胞中铁色素的保留表明氟化物改变成釉细胞中铁转运的细胞机制。铁对于细胞功能很重要，但铁过量会导致不稳定铁池增加，从而导致自由基形成，从而产生氧化应激。因此，铁的细胞调节对于细胞生长和存活至关重要。在初步研究中，我们发现，随着成熟成釉细胞中铁保留的增加，铁结合蛋白铁蛋白也增加。铁蛋白以结晶形式与铁结合，保护细胞免受铁相关的氧化应激，并可被核因子 kappa B (NF?B) 上调。该提案的总体目标是研究氟化物增强成釉细胞中铁保留的细胞机制，以及该机制在调节成熟阶段成釉细胞氧化应激中的作用。这一目标将通过以下两个具体目标来实现。目标 1) 确定氟化物如何改变成熟阶段成釉细胞的铁吸收和储存；目标 2) 确定氟化物如何调节成熟阶段成釉细胞的氧化还原状态。了解氟化物对铁稳态的潜在生物效应将产生有关氟斑牙背后机制的重要信息，这可能导致确定新的治疗方法以降低氟斑牙的发病率。