Enamel with overexpressed ameloblastin

牙釉质过度表达成釉细胞

• 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
• 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

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.

项目总结/摘要 磨牙-切牙矿化不足（MIH）在地球仪各地的儿童中非常普遍，影响他们的 乳牙和恒牙。受影响的牙釉质有白垩色至黄色的病变， 较少的矿化导致增加的龋齿易感性、釉质破裂、美学问题和敏感 牙齿.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 这阻碍了精确的靶向治疗的发展。MIH的一个显著特点是 缺陷的分界，使受影响和未受影响的釉质位于相邻，突然 矿物密度的变化。这一特点与氟中毒形成鲜明对比，氟中毒的特点是弥漫性的， 矿化不足成釉蛋白是形成正常釉质所必需的釉质蛋白之一 阵在缺乏成釉蛋白的情况下，釉质发育不全，称为成釉细胞。当 当成釉蛋白表达过多时，在小鼠中釉质显示出分界的低矿化损伤。 MIH的病因尚不清楚。目前正在讨论接触环境毒物的问题。的 MIH牙齿的釉质的特征在于釉质蛋白质和酶的失衡， 矩阵。 本研究的假设是成釉蛋白过度表达导致了分界和 通过酶失衡导致的低矿化病变。拟议的目标将确定以下途径： Ambn过度表达和酶不足引起的界限性釉质矿化不足。在SA 1中 我们将确定是否分界，低矿化病变是由酶不足引起的， 成釉蛋白过度表达。在SA 2中，我们将确定转录组和转录调控， Ambn和过表达Ambn在成釉细胞使用培养的初级釉器官上皮，称为 “成釉细胞样”。在SA 3中，小鼠模型的发现将转化为微创MIH 处理方案涉及调节和渗透多孔的低矿化牙釉质。最后， 该项目将通过将基础和临床前研究转化为临床研究来弥补MIH治疗的差距 research.