Characterization of DMP1 a dentin phosphoprotein

牙本质发生是一个动态过程，涉及细胞和细胞外基质的级联反应。 细胞外事件特定的交互事件，如细胞-细胞、细胞-基质和 基质-基质负责成牙本质细胞的分化和 矿化的牙本质基质矿化过程中的问题是显而易见的 在许多牙科疾病中。成功的牙本质再生和修复 牙科学依赖于将成牙本质细胞前体细胞募集到所跟踪的部位的能力 通过这些细胞的成熟过程，基质沉积， 有机基质的矿化。非胶原酸性蛋白已被 假定在从头矿物成核中起调节作用，调节 羟基磷灰石晶体尺寸以及其形态。牙本质基质蛋白1 （DMP 1）是我们首先从矿化细胞中克隆的细胞外基质， 牙本质基质DMP 1通常是阴离子的，具有多个钙结合位点 并被认为通过使羟基磷灰石成核来促进矿化。一个 有趣的发现，我们已经报告的是，DMP 1可以执行多个 功能协调发展的发现非磷酸化的DMP 1易位到细胞核 在成牙本质细胞的早期分化过程中， 生物矿化特异性基因的表达。的中心假设 研究表明，DMP 1在糖尿病发病过程中发挥着重要而独特的作用。 成牙本质细胞的成熟，导致矿化牙本质的形成。 因此，提出了三个具体目标，以追究责任机制 对于DMP 1介导的成牙本质细胞分化和矿化基质形成： (1)探讨成牙本质细胞分化过程中DMP 1的细胞靶点; 探讨DMP 1基因在成牙本质细胞分化中的分子机制; (3)目的探讨DMP 1能否诱导干细胞向成牙本质细胞分化。 了解矿化过程对生物医学 和牙科领域，因为正常生物矿化的破坏可能导致 病理性钙化或脱矿过程。远景目标 是了解DMP 1发挥独特作用的调节机制， 在牙本质矿化中的作用

Dentinogenesis is a dynamic process that involves a cascade of cellular and extracellular events. Specific interactive events like cell-cell, cell-matrix and matrix-matrix are responsible for odontoblast differentiation and the assembly of the mineralized dentin matrix. Problems in the mineralization process are evident in a number of dental pathologies. Successful dentin regeneration and repair in dentistry relies on the ability to recruit odontoblast precursors to the site followed by maturation process of these cells, matrix deposition and ultimately mineralization of the organic matrix. Noncollagenous acidic proteins have been postulated to play a regulatory role in de novo mineral nucleation, regulating hydroxyapatite crystal size as well as its morphology. Dentin matrix protein 1 (DMP1) is an extracellular matrix that was first cloned by us from the mineralized dentin matrix. DMP1 is typically anionic and has multiple calcium binding sites and is thought to promote mineralization by nucleating hydroxyapatite. An intriguing finding that we have reported is that DMP1 can perform multiple functions. Non-phosphorylated DMP1 was found to translocate to the nucleus during early differentiation of odontoblasts and function in regulating the expression of biomineralization-specific genes. The central hypothesis of the proposed studies is that DMP1 plays an important and unique role during maturation of odontoblasts, leading to the formation of mineralized dentin. Therefore 3 specific aims are proposed to pursue the mechanisms responsible for DMP1 mediated odontoblast differentiation and mineralized matrix formation: (1) To study the cellular targets of DMP1 during odontoblast differentiation; (2) To elucidate the molecular mechanisms of DMP1 gene on odontoblast differentiation; (3) To determine if DMP1 can induce odontoblast lineage in stem cells. Understanding the mineralization process is important to the biomedical and dentistry fields as disruption of normal biomineralization can lead to pathological calcification or demineralization process. The long-term goal is to understand the regulatory mechanism by which DMP1 plays a unique role in dentin mineralization.