Matrix Protein Regulation of Enamel Mineral Formation

牙釉质矿物质形成的基质蛋白调节

• 批准号: 7104885
• 负责人: HENRY C MARGOLIS
• 金额: $ 40.55万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7104885
• 关键词: X ray crystallography; acidity /alkalinity; adsorption; amelogenin; calcification; calcium phosphate; crystallization; dental development; enamelin; endopeptidases; extracellular matrix proteins; hydroxyapatites; infrared spectrometry; interferometry; intermolecular interaction; light scattering; low angle X ray diffraction analysis; molecular assembly /self assembly; neutron diffraction; precipitation; protein binding; protein structure function; scanning transmission electron microscopy; tooth enamel

The purpose of this project is to elucidate the structure and mechanism of formation of higher order assemblies of enamel matrix proteins and their influence on mineralization and crystal organization in vitro. We propose that organized mineral stuctures are generated within organized super-assemblies of matrix proteins in cooperation with other macromolecules that guide crystal growth and shape. Our working hypothesis is that higher order assemblies of full-length amelogenin, in association with soluble acidic proteins (e.g., enamelin and ameloblasrin), regulate the nucleation, growth, shape, and arrangement of initial enamel mineral crystals. Under appropriate mineralizing conditions, such assemblies support the formation of parallel arrays of very thin ribbons of enamel mineral. The growth of these enamel ribbons in thickness and width is immediately inhibited by soluble hydrophobic enamel proteins (e.g. sparingly soluble amelogenins) which adsorb onto specific faces of the growing crystals. It is further hypothesized that the subsequent onset of growth of these mineral ribbons during tissue maturation is controlled by the degradation of these enamel protein inhibitors by specific enamel proteinases. To improve our understanding of how matrix proteins regulate mineralization in tissues like enamel, we propose to characterize specific enamel matrix components with respect to their ability to form higher-order assemblies that ultimately regulate organized mineralization. Specifically, we propose to characterized the ability of key enamel matrix proteins to bind to mineral surfaces (Aim 1), to regulate crystal shape and kinetics of crystal growth (Aim 2), and to induce calcium phosphate formation in vitro (Aim 3). Importanly, these findings; will be integrated with biophysical studies to determine the structure and mechanism of formation of proposed higher order assemblies of the full-length amelogenin (Aim 4) and the mechanism by which such assemblies regulate the formation of organized mineral structures, similar to that of dental enamel (Aim 5). Long term, such information should provide new insights for the development of bio-inspired materials and novel approaches for mineralized tissue repair and regeneration.

该项目的目的是阐明搪瓷基质蛋白高阶组合形成的结构和机理及其对矿化和晶体组织的影响。我们提出，与指导晶体生长和形状的其他大分子合作，在有组织的基质蛋白的有组织的超级组件中产生有组织的矿物构成。我们的工作假设是，全长蛋白质蛋白的高阶组件与可溶性酸性蛋白（例如，搪瓷蛋白和杏仁糖蛋白）相关，调节了初始陶器矿物矿物质晶体的成核，生长，形状和排列。在适当的矿化条件下，这种组件支持形成搪瓷矿物质非常薄的丝带的平行阵列。这些牙釉质丝带在厚度和宽度上的生长立即被吸附到生长晶体的特定面上的可溶性疏水搪瓷蛋白（例如，稀疏可溶蛋白）的生长。进一步假设，这些矿物缎带随后在组织中的生长发作 这些搪瓷蛋白抑制剂通过特定的搪瓷蛋白酶降解来控制成熟。为了提高我们对基质蛋白如何调节牙釉质等组织中矿化的理解，我们建议表征特定的牙釉质基质成分相对于它们形成最终调节有组织矿化的高阶组件的能力。具体而言，我们建议表征关键的搪瓷基质蛋白与矿物表面结合的能力（AIM 1），调节晶体生长的晶体形状和动力学（AIM 2），2），AIM 2），2） 并在体外诱导磷酸钙形成（AIM 3）。这些发现很重要。将与生物物理研究集成，以确定全长氨基蛋白蛋白的高阶高阶组合形成的结构和机制（AIM 4）以及这种组件调节有组织矿物结构的形成，类似于牙齿搪瓷的机制（AIM 5）。长期，此类信息应为开发生物启发的材料的开发和矿化组织修复和新颖方法提供新的见解 再生。