VESICLES AND ENDOCHONDRAL BONE FORMATION

这个项目的主要目标是阐明 导致羟基磷灰石形成和生长的事件 脊椎动物矿化组织基质中的晶体，包括 牙釉质、牙本质、钙化软骨和骨。的矿化 这些组织是由专门的细胞进行存款矿物质 离子到预先形成的有机基质上，并且其特征在于严格 特定基因表达的时空调控 产品.所有脊椎动物矿化组织的唯一共同成分 是钙和磷酸盐离子和碱性磷酸酶。而 本研究的开始将集中于碱性磷酸酶， 基质囊泡，该项目的最终目标将是了解 在囊泡或细胞表面引发的事件如何导致 基质大分子的矿化，主要是胶原蛋白。的 在这个提议中的实验将调查描述 细胞、囊泡和基质成分的不同功能作用， 基质囊泡依赖性基质矿化。将对假设进行检验 关于特定MV和基质成分的重要性， 囊内与囊外矿物质形成意义， 包括钙在内的可溶性中间体的代谢 磷酸根离子簇。实验提出了调查积极的 负调制离子团簇的生长和发展， 沉积和生长胚晶。 目前，我们的 对发生的事件之间的初始事件矿化的认识 在基质囊泡内和周围以及在胶原蛋白内和周围 纤维 本提案旨在通过发现 化学物种和生化机制，可以桥接它。因此， 我们认为二尖瓣是钙化的必要部分， 机器，我们是由我们的调查，以及其他 实验室，把我们的注意力集中在基质囊泡的相互作用 与矩阵。有了这些工具，我们可以方便地进行这项研究， 准备将长期冲突的概念结合成一个统一的假设。

The major goal of this project is to elucidate the precise sequence of events which results in the formation and growth of hydroxyapatite crystals in the matrix of vertebrate mineralized tissues which include dental enamel, dentin, calcified cartilage and bone. The mineralization of these tissues is carried out by specialized cells which deposit mineral ions onto a preformed organic matrix, and is characterized by strict spatial and temporal regulation of the expression of specific gene products. The only components common to all vertebrate mineralized tissues are calcium and phosphate ions and the enzyme, alkaline phosphatase. While the beginning of this investigation will focus on alkaline phosphatase and matrix vesicles, the ultimate target of the project will be to understand how events initiated at the vesicle or cell surface result in the mineralization of matrix macromolecules, principally collagens. The experiments in this proposal will investigate hypotheses which delineate distinct functional roles for cell, vesicle and matrix constituents in matrix vesicle-dependent matrix mineralization. Hypotheses will be tested concerning the importance of specific MV and matrix components, the significance of intravesicular vs. extravesicular mineral formation and the metabolism of soluble intermediates which may include calcium phosphate ion-clusters. Experiments are proposed to investigate positive and negative modulation of ion-cluster growth and development and deposition and growth embryo crystals. At present, a gap exists in our knowledge of the initial events mineralization between events which occur in and around matrix vesicles and those occur in and around collagen fibrils. This proposal is aimed at crossing that gap by discovering the chemical species and biochemical mechanisms which may bridge it. Thus, while we believe that MV are a necessary part of the calcification machinery, we are led by our investigations, as well as those of other laboratories, to focus our attention on the interaction of matrix vesicles with the matrix. With the tools in hand to facilitate this study, we are poised to join long clashing conceptions into a unified hypothesis.