BAG-75: UNIQUE MARKER OF PRIMARY BONE FORMATION

BAG-75:初级骨形成的独特标记

基本信息

  • 批准号:
    6642816
  • 负责人:
  • 金额:
    $ 14.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2002
  • 资助国家:
    美国
  • 起止时间:
    2002-09-01 至 2005-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Primary bone is defined morphologically as bone formed directly from soft mesenchymal tissue without a calcified cartilage or mineralized precursor stage. Long bones develop postnatally by the apposition of primary bone upon cartilaginous remnants in the primary spongiosa, while all or parts of the frontal, parietal, occipital, temporal, maxilla, and mandible bones of the craniofacial system form and remain as primary bone. Research on primary bone has received less emphasis in the past and the true extent of cellular and biochemical differences between primary and lamellar bone are unknown. While lamellar bone represents the mature structure, primary bone is the precursor of lamellar bone-capable of being formed de novo. Primary bone can be distinguished from lamellar (cortical) bone on the basis of the faster speed of its deposition, exquisite spatial patterning and mineralization, its apparent specific enrichment in acidic phosphoprotein BAG-75, and its increased sensitivity to applied biomechanical forces and systemic hormones. We propose that BAG-75, through its strong propensity to self-associate into supramolecular microfibrillar complexes, serves as a structural framework defining the volume of primary bone matrix to be subsequently calcified. The goal of this proposal is to address the hypothesis that BAG-75 (bone acidic glycoprotein-75) is a unique gene product whose expression is restricted to active de novo calcification reactions, and, which contains more than 40 casein kinase phosphorylation sites, one or more polyglutamic acid calcium-binding motifs, N- and O-linked oligosaccharide attachment sites, and a repetitive modular primary structure facilitating home-and heteropolymeric associations required for formation and mineralization of primary bone. This project fits two main objectives of the R2 1 mechanism: to support innovative and high-risk research relevant to the primary research mission areas of NIDCR, and, initial development of a line of research upon which significant future studies can be based. For example, if a BAG-75 framework serves a key organizational role, a surface coating of BAG-75 could improve the stability of dental and orthopedic implants; 8-9 percent of the 1 37,000 hip implants in the U.S. each year require revision surgery within 5-10 years. We envision that a BAG-75 coated, non-cemented implant would self-associate with host-derived BAG-75 to form a seamless natural framework leading to deposition of other matrix components and mineralization within submicron distances of the implant surface--improving functional longevity of implants. Since primary bone is capable of being formed de novo, future determination of the BAG-75 promoter structure could form the basis of a new gene therapy approach to reverse losses in trabecular bone connectivity and alveolar bone volume with aging by targeting local stimulatory agents to primary bone osteoprogenitor cells expressing BAG-75, thus enhancing bone volume and restoring lost trabecular connectivity. Stimulation of appositional formation by lamellar bone would not be expected to have the same effect. These future functional studies require determination of the BAG-75 cDNA sequence.
描述(由申请人提供):初级骨在形态学上定义为 直接由软间质组织形成的骨,没有钙化软骨 或矿化前体阶段。长骨在出生后发育 初级骨与初级骨中的软骨残余物并置 海绵体,而额叶、顶叶、枕叶、颞叶的全部或部分, 颅面系统的上颌骨和下颌骨形成并保持为 主要骨。过去对原生骨的研究较少受到重视 以及原代和原代细胞之间细胞和生化差异的真实程度 板层骨未知。虽然板层骨代表了成熟的结构, 初生骨是板层骨的前体,能够从头形成。 初级骨与板层(皮质)骨的区别在于: 其沉积速度更快,空间图案更精致 矿化,其酸性磷蛋白的明显特异性富集 BAG-75 及其对所施加的生物力学力的敏感性增加 全身激素。我们建议 BAG-75 通过其强烈的倾向 自缔合成超分子微纤维复合物,作为 结构框架定义了随后钙化的初级骨基质的体积。该提案的目标是解决假设 BAG-75(骨酸性糖蛋白75)是一种独特的基因产物,其 表达仅限于活跃的从头钙化反应,并且, 含有40多个酪蛋白激酶磷酸化位点,1个或多个 聚谷氨酸钙结合基序、N-和O-连接寡糖 附着点,以及重复的模块化主结构,方便家庭和 形成和矿化所需的杂聚缔合 主要骨。该项目符合 R2 1 机制的两个主要目标: 支持与初级研究相关的创新和高风险研究 NIDCR 的任务领域,以及一系列研究的初步发展 未来的重要研究可以以此为基础。例如,如果 BAG-75 框架起着关键的组织作用,BAG-75 的表面涂层可以 提高牙科和骨科植入物的稳定性; 1 的 8-9% 美国每年有 37,000 个髋关节植入物需要在 5-10 天内进行翻修手术 年。我们设想 BAG-75 涂层的非骨水泥植入物将 与宿主衍生的 BAG-75 自关联,形成无缝的自然框架 导致其他基质成分的沉积和矿化 种植体表面的亚微米距离——提高种植体的功能寿命 植入物。由于初级骨能够从头形成,未来 BAG-75启动子结构的确定可以为新的 基因治疗方法可逆转小梁骨连接性的损失 通过靶向局部刺激剂来改变牙槽骨体积随衰老的变化 原代骨骨祖细胞表达 BAG-75,从而增强骨骼 体积并恢复失去的小梁连接。同位刺激 板层骨的形成预计不会产生相同的效果。这些 未来的功能研究需要确定 BAG-75 cDNA 序列。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Biomineralization of bone: a fresh view of the roles of non-collagenous proteins.
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JEFFREY Paul GORSKI其他文献

JEFFREY Paul GORSKI的其他文献

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{{ truncateString('JEFFREY Paul GORSKI', 18)}}的其他基金

Eleventh International Conference on the Chemistry and Biology of Mineralized Tis
第十一届国际矿化钛化学与生物学会议
  • 批准号:
    8459213
  • 财政年份:
    2013
  • 资助金额:
    $ 14.5万
  • 项目类别:
MINERALIZATION OF PRIMARY BONE
原生骨的矿化
  • 批准号:
    7125520
  • 财政年份:
    2005
  • 资助金额:
    $ 14.5万
  • 项目类别:
MINERALIZATION OF PRIMARY BONE
原生骨的矿化
  • 批准号:
    7432628
  • 财政年份:
    2005
  • 资助金额:
    $ 14.5万
  • 项目类别:
MINERALIZATION OF PRIMARY BONE
原生骨的矿化
  • 批准号:
    6959061
  • 财政年份:
    2005
  • 资助金额:
    $ 14.5万
  • 项目类别:
MINERALIZATION OF PRIMARY BONE
原生骨的矿化
  • 批准号:
    7237208
  • 财政年份:
    2005
  • 资助金额:
    $ 14.5万
  • 项目类别:
BAG-75: UNIQUE MARKER OF PRIMARY BONE FORMATION
BAG-75:初级骨形成的独特标记
  • 批准号:
    6464697
  • 财政年份:
    2002
  • 资助金额:
    $ 14.5万
  • 项目类别:
MOLECULAR GENETICS OF HYPODONTIA
牙齿发育不全的分子遗传学
  • 批准号:
    2014980
  • 财政年份:
    1997
  • 资助金额:
    $ 14.5万
  • 项目类别:
CARBOHYDRATE RECEPTORS IN OSTEOCLAST FUNCTION
破骨细胞功能中的碳水化合物受体
  • 批准号:
    2132377
  • 财政年份:
    1994
  • 资助金额:
    $ 14.5万
  • 项目类别:
CARBOHYDRATE RECEPTORS IN OSTEOCLAST FUNCTION
破骨细胞功能中的碳水化合物受体
  • 批准号:
    2132375
  • 财政年份:
    1994
  • 资助金额:
    $ 14.5万
  • 项目类别:
IN VIVO/IN VITRO STUDIES OF BONE ACIDIC GLYCOPROTEIN-75
骨酸性糖蛋白-75 的体内/体外研究
  • 批准号:
    3437176
  • 财政年份:
    1991
  • 资助金额:
    $ 14.5万
  • 项目类别:

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