BONE SIALOPROTEIN--EXPRESSION AND ROLE IN MINERALIZATION

描述（改编自研究者摘要）：骨唾液蛋白（BSP） 是骨细胞外基质（ECM）的非胶原成分， 在生物矿化中扮演着重要的角色。 这项建议会 建立BSP在骨中表达的核调控机制， 通过实现以下具体目标，发挥其在矿化中的作用：目标1。 确定BSP基因和相关核蛋白的5 '调控区 骨和ECM特异性表达所必需的。 申请人提议， 由ECM提供的信号对于组织特异性表达 BSP以及ECM调节BSP和其他成骨细胞相关基因产物 通过共同的核机制，包括激活/诱导 特定的核蛋白。 小鼠BSP基因启动子和/或内含子 序列将用于定义DNA序列和相关的核 ECM依赖性和组织特异性表达所必需的蛋白质。 目标二。 确定BSP在成骨细胞介导的生物矿化中的作用。 战略规划编制局 几个属性一致，它发挥了重要作用， 包括使羟基磷灰石成核能力的矿化的引发 体外晶体形成。 然而，它在成矿作用中的作用尚未得到证实。 在类似骨头的环境中进行了检查。 使用成骨细胞培养 系统，形成和矿化骨样ECM，计划的研究将使用 多种方法来阐明BSP在矿化中的作用，包括 抗体阻断实验、反义RNA和强制表达。 网站 定向诱变将确定BSP分子的关键区域 活动所必需的。 该项目将确定一个共同机制， 由此成骨细胞ECM控制BSP的组织特异性表达， 其他成骨细胞蛋白的基本知识，了解病理 破坏基质完整性或合成的条件，如牙周炎， 疾病、类风湿性关节炎、骨生成障碍和骨质疏松症。 通过 确定BSP在生理矿化研究中的作用， 解决长期存在的关于这一角色的争议 磷蛋白在骨形成中的作用 了解骨骼和牙齿中其他相关蛋白质的功能， 并提供了一种在疾病状态下调节矿化的方法。

DESCRIPTION (Adapted from investigator's Abstract): Bone sialoprotein (BSP) is a noncollagenous component of bone extracellular matrix (ECM) considered to play a fundamental role in biomineralization. This proposal will establish the nuclear mechanism regulating BSP expression in bone and define its role in mineralization by achieving the following specific aims: Aim 1. Define 5'-regulatory regions of the BSP gene and related nuclear proteins necessary for bone and ECM-specific expression. The applicant proposes that signals provided by the ECM are essential for tissue-specific expression of BSP and that ECM regulates BSP and other osteoblast-related gene products through a common nuclear mechanism involving the activation/induction of specific nuclear proteins. The mouse BSP gene promoter and/or intronic sequences will be used to define DNA sequences and associated nuclear proteins necessary for ECM-dependent and tissue-specific expression. Aim 2. Establish the role of BSP in osteoblast-mediated biomineralization. BSP has several properties consistent with it playing an important role in the initiation of mineralization including ability to nucleate hydroxyapatite crystal formation in vitro. However, its role in mineralization has not yet been examined in a bone-like environment. Using an osteoblast cell culture system that forms and mineralizes a bone-like ECM, planned studies will use multiple approaches to elucidate the role of BSP in mineralization including antibody blocking experiments, antisense RNAs and forced expression. Site directed mutagenesis will then define critical regions of the BSP molecule necessary for activity. This project will identify a common mechanism whereby osteoblast ECM controls the tissue-specific expression of BSP and other osteoblast proteins essential knowledge for understanding pathological conditions that disrupt matrix integrity or synthesis such as periodontal disease, rheumatoid arthritis, osteogenesis imperfecta and osteoporosis. By defining the role of BSP in physiological mineralization studies will resolve a long standing controversy concerning the role/s of this phosphoprotein in bone formation develop an approach that could be applied to understanding the function of other related proteins in bones and teeth, and provide a means for regulating mineralization in diseased states.