Enamel with overexpressed ameloblastin

项目摘要/摘要 磨牙切牙矿化(MIH)是一种在全球儿童中高度流行的疾病，影响他们的 乳牙和恒牙。受影响的牙釉质有白垩色到黄色的损害，边界清楚， 矿化较少会增加龋齿易感性、牙釉质脱落、审美问题和敏感性 牙。虽然这些病变的治疗和管理是具有挑战性的，但MIH的病理生理学是 未知，阻碍了精确的、有针对性的治疗的发展。MIH的一个显著特点是 缺陷的界定，使受影响的牙釉质和未受影响的牙釉质位于相邻的位置，具有陡峭的 矿物密度的变化。这一特征与以弥漫性为特征的氟中毒形成鲜明对比 低矿化。成釉蛋白是正常牙釉质所必需的釉质蛋白之一。 队形。在没有成釉蛋白的情况下，釉质发育不全，称为成釉不全。什么时候 成釉蛋白表达过多，小鼠牙釉质呈分界性、矿化程度低的病变。 MIH的病因尚不清楚。目前讨论的是暴露在环境毒物中。这个 MIH牙釉质的特点是釉质蛋白质和降解牙釉质的酶的失衡 麦特丽克斯。 这项研究的假设是成釉蛋白的过度表达导致 酶失衡所致的低矿化病变。拟议的目标将定义 AMBN过度表达和酶不足所致的釉质矿化不足。在SA1中 我们将确定分界性、低矿化性损害是否由相对于以下方面的酶不足引起 成釉蛋白过度表达。在SA2中，我们将确定转录组学和转录调控 AMBN及其在原代成釉细胞中过表达的AMBN “成釉细胞”。在SA3中，小鼠模型的发现将被转化为微创的MIH 治疗方案用于调节和渗透多孔的、低矿化的牙釉质。最终， 该项目将通过将基础和临床前研究转化为临床，弥合MIH治疗方面的差距 研究。

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.