MINERALIZATION STUDIES RELATED TO ORAL BIOLOGY

与口腔生物学相关的矿化研究

• 批准号: 6164400
• 负责人: HARRISON CLARKE ANDERSON
• 金额: $ 24.36万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-03-01 至 2002-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6164400
• 关键词: P glycoprotein; adenosinetriphosphatase; alkaline phosphatase; apoptosis; bone morphogenetic proteins; bone sialoprotein; calcification; calpain; cartilage; cell growth regulation; dentin; enzyme activity; extracellular matrix proteins; laboratory mouse; laboratory rat; membrane biogenesis; membrane proteins; osteocalcin; osteonectin; osteopontin; protein biosynthesis; protein glutamine gamma glutamyltransferase; protein structure function; tissue /cell culture; western blottings

The proposed study will focus on matrix vesicles (MVs) which play an initiating role in mineralization of teeth and bones. MVs are submicroscopic extracellular, membrane-invested particles that serve as the initial site of calcification in dentin, growth plate cartilage and developing bone. Our lab was involved in the first identification, isolation and characterization of MVs. We and others have provided evidence that MV phosphatases, including alkaline phosphatase (ALP), and ATPase are involved in MV mineralization. Furthermore, these phosphatase are integrated into the MV membrane which mineral first appears, suggesting a critical role for components of the MV membrane in initiating calcification. Our specific aims are directed toward an increased understanding of the molecular and structural organization of the MV membrane and sap with emphasis on identify and localizing major constitutive proteins, testing the function of MVs, and studying the regulation of MV biogenesis by cultured bone or cartilage progenitor cells. Specific aims: 1) Identification of major MV proteins that may play a role in calcification, including non-collagenous proteins of bone (bone sialoprotein, osteopontin, osteonectin, osteocalcin), calpain, and P-glycoprotein. 2) Experimental calcification of isolated MVs to further elucidate the role of vesicle phosphatases, especially ALP and ATPase, plus other integral MV proteins in the calcification mechanism. 3) a study of the mechanism of MV biogenesis by plasma membrane budding, examining possible regulators of MV biogenesis (e.g. the bone morphogenetic proteins) and the relation of MV biogenesis to differentiation and programmed cell death (apoptosis). This is a fundamental study of the mechanism by which dental and skeletal forms of mineralization are initiated. New knowledge of matrix vesicle calcification can be applied to a broad range of topics including specific diseases in which abnormal calcification occurs.

拟议的研究将重点介绍发挥作用的基质囊泡（MV） 在牙齿和骨骼的矿化中发挥作用。 MV是 亚微镜细胞外，膜侵入的颗粒，作为用作 牙本质中钙化的初始位点，生长板软骨和 发育骨骼。我们的实验室参与了第一个识别， MV的隔离和表征。 我们和其他人提供了 证据表明MV磷酸酶，包括碱性磷酸酶（ALP）和 ATPase参与MV矿化。此外，这些磷酸酶 被整合到MV膜中，首先出现矿物质， 提出了MV膜组件中的关键作用 启动钙化。我们的具体目标是针对 对分子和结构组织的了解增加 MV膜和SAP，重点是识别和本地化专业 组成蛋白，测试MV的功能并研究 通过培养的骨头或软骨祖细胞调节MV生物发生 细胞。具体目的：1）鉴定可能的主要MV蛋白 在钙化中起作用，包括骨骼的非胶原蛋白 （骨唾液蛋白，骨桥蛋白，骨蛋白蛋白蛋白蛋白，骨钙素），钙蛋白酶和钙蛋白酶和 P-糖蛋白。 2）实验钙化分离的MV以进一步 阐明囊泡磷酸酶的作用，尤其是ALP和ATPase， 加上钙化机制中的其他积分MV蛋白。 3）a 研究通过质膜萌芽的MV生物发生机制的研究， 检查可能的MV生物发生调节剂（例如 形态发生蛋白）和MV生物发生与 分化和程序性细胞死亡（凋亡）。 这是对牙齿和牙齿和 开始矿化的骨骼形式。矩阵的新知识 囊泡钙化可以应用于广泛的主题 包括发生异常钙化的特定疾病。