Enamel with overexpressed ameloblastin

牙釉质过度表达成釉细胞

基本信息

批准号：
10667251
负责人：
Yong-Hee Patricia Chun
金额：
$ 36.04万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2023-09-04
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10667251
关键词：
ATAC-seq Address Adherens Junction Affect Ameloblasts Amelogenesis Amelogenesis Imperfecta Basic Science Child Clinical Research Complex Country Crystallization Defect Dental Dental Enamel Dental caries Development Diffuse Distal Enamel Formation Enamel Organ Enzymes Epithelial Esthetics Exposure to Functional disorder Hardness Health Height Histology Hydroxyapatites Immunohistochemistry In Situ Hybridization In Vitro Incisor Infiltration Ion Transport Lesion MMP-20 Maturation-Stage Ameloblast Membrane Minerals Molecular Weight Mus Pathogenesis Pathway interactions Phosphoric Acids Population Porosity Positioning Attribute Predisposition Process Proteins Research Residual state Serum Spottings Surface Tight Junctions Tissues Tooth Demineralization Tooth structure Toxic Environmental Substances Transcriptional Regulation Translating Treatment Protocols Western Blotting ameloblastin bioinformatics tool claudin-1 protein conditioning deciduous tooth density effective therapy fluorosis mRNA Expression malformation matrigel microCT minimally invasive mouse model nano overexpression permanent tooth pre-clinical research preservation protein expression public health relevance reconstitution scaffold single-cell RNA sequencing targeted treatment transcription factor transcriptome

项目摘要

PROJECT SUMMARY/ABSTRACT Molar-Incisor Hypomineralization (MIH) is a highly prevalent in children all around the globe affecting their primary and permanent teeth. The affected enamel has chalky to yellow lesions that are demarcated and less mineralized causing increased caries susceptibility, enamel breakout, esthetic concerns and sensitive teeth. While the treatment and management of these lesions are challenging, the pathophysiology of MIH is not known, hampering the development of a precise, targeted therapy. A striking feature of MIH is the demarcation of defects, such that affected and unaffected enamel are located adjacently, with abrupt changes in mineral density. This feature is in stark contrast to fluorosis which is characterized by diffuse hypomineralization. Ameloblastin is one of the essential enamel proteins required for proper enamel formation. In the absence of ameloblastin enamel is hypoplastic, known as amelogenesis imperfecta. When ameloblastin is expressed too much, the enamel displays demarcated, hypomineralized lesions in mice. The pathoetiology of MIH is unknown. Exposure to environmental toxicants are currently discussed. The enamel of MIH teeth is characterized by an imbalance of enamel proteins and enzymes degrading the m atrix. The hypothesis of this research is that ameloblastin overexpression causes demarcated and hypomineralized lesions through enzymatic imbalance. The proposed Aims will define the pathways of demarcated enamel hypomineralization caused by Ambn overexpression and insufficient enzyme. In SA1 we will determine if demarcated, hypomineralized lesions are caused by insufficient enzyme relative to ameloblastin overexpression. In SA2, we will determine the transcriptome and transcriptional regulation of Ambn and overexpressed Ambn in ameloblasts using cultured primary enamel organ epithelium, termed ‘ameloblastoids’. In SA3, findings from the mouse model will be translated into a minimally invasive MIH treatment protocol addressing conditioning and infiltrating the porous, hypomineralized enamel. Ultimately, this project will bridge the gap in MIH treatment by translating basic and preclinical research into clinical research.

项目概要/摘要磨牙-切牙矿化低下 (MIH) 在全球儿童中非常普遍，影响他们的受影响的牙釉质有明显的白垩色至黄色永久性病变。矿化程度较低，导致龋齿易感性增加、牙釉质破裂、美观问题和敏感虽然这些病变的治疗和管理具有挑战性，但 MIH 的病理生理学是很复杂的。 MIH 的一个显着特征是其未知性，阻碍了精确靶向治疗的发展。缺陷的划分，使受影响和未受影响的牙釉质相邻，并具有突然的这一特征与氟中毒形成鲜明对比，氟中毒的特点是弥漫性。成釉素是正常牙釉质所需的必需牙釉质蛋白之一。在缺乏成釉细胞的情况下，牙釉质发育不全，称为釉质形成不全。由于成釉细胞蛋白表达过多，小鼠牙釉质出现明显的、矿化不足的病变。 MIH 的病理学尚不清楚，目前正在讨论环境毒物的暴露。 MIH 牙釉质的特点是釉质蛋白和酶的不平衡，会降解牙釉质。矩阵。这项研究的假设是成釉细胞过度表达会导致划界和所提出的目标将确定通过酶失衡导致的矿化不足的病变。由 Ambn 过度表达和 SA1 酶不足引起的划界牙釉质矿化不足。我们将确定界定的、矿化不足的病变是否是由相对于酶不足引起的在 SA2 中，我们将确定转录组和转录调控。使用培养的原代釉质器官上皮细胞中的 Ambn 和过度表达的 Ambn，称为 “成釉细胞”在 SA3 中，小鼠模型的研究结果将转化为微创 MIH。治疗方案解决了调理和渗透多孔、矿化不足的牙釉质的问题。该项目将通过将基础和临床前研究转化为临床来缩小 MIH 治疗的差距研究。