Characterization of DMP1 a dentin phosphoprotein

牙本质形成是一个动态的过程，它涉及一系列细胞和 细胞外事件。特定的交互事件，如细胞-细胞、细胞-矩阵和 基质-基质负责成牙本质细胞的分化和组装 矿化的牙本质基质。矿化过程中的问题是显而易见的 在许多牙科病理中。成功的牙本质再生和修复 牙科依赖于将成牙本质细胞前体细胞招募到后续部位的能力 通过这些细胞的成熟过程，基质沉积，最终 有机基质的矿化作用。非胶原酸性蛋白已经被 被认为在从头开始的矿物成核中发挥调节作用，调节 羟基磷灰石的晶体大小及其形态。牙本质基质蛋白1 DMP1是我们首次从矿化细胞中克隆的一种细胞外基质 牙本质基质。DMP1通常是阴离子的，有多个钙结合部位 被认为是通过使羟基磷灰石成核来促进矿化。一个 我们已经报道的有趣的发现是，DMP1可以执行多个 功能。非磷酸化的DMP1被发现移位到细胞核 成牙本质细胞早期分化过程中的调控作用 生物矿化特异性基因的表达。的核心假说 建议的研究表明，DMP1在体内发挥着重要而独特的作用 成牙本质细胞成熟，形成矿化的牙本质。 因此，提出了三个具体目标，以追究责任机制 对于DMP1介导的成牙本质细胞分化和矿化基质形成： (1)研究DMP1在成牙本质细胞分化过程中的细胞靶点；(2) 阐明DMP1基因在成牙本质细胞分化中的分子机制； (3)探讨DMP1能否诱导干细胞向成牙本质细胞分化。 了解成矿过程对生物医学具有重要意义 而牙科领域的正常生物矿化中断可能会导致 病理性钙化或脱矿过程。长期目标 是为了了解DMP1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.