Nature of Bone Mineral: Inception, Maturation, Aging

骨矿物质的性质：起始、成熟、老化

• 批准号: 6791314
• 负责人: MELVIN J GLIMCHER
• 金额: $ 48.11万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-11 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6791314
• 关键词: X ray crystallography; animal tissue; atomic force microscopy; bone; bone density; bone imaging /visualization /scanning; calcium; chemical structure; chick embryo; clinical research; crystallization; electron microscopy; fluorescence spectrometry; human tissue; infrared spectrometry; laboratory rabbit; mathematical model; microspectrophotometry; minerals; normal ossification; nuclear magnetic resonance spectroscopy; phosphates; tissue /cell culture

DESCRIPTION (provided by applicant): Functions of biological inorganic crystals depend on their size, shape, long- and short-range order, chemical composition, specific ion environments, and spatial and chemical relationships with extracellular matrices and cells. Bone functions include contributions to mechanical characteristics, ion reservoir to maintain homeostasis of extra cellular fluids, and interactions with cells, all of which control their interactive properties and thus their mechanical and physiological roles. Data from in vitro 31P NMR, spectroscopy and imaging and in vivo experiments in living animals (eventually humans) will provide true 3-D volumetric bone mineral and bone matrix (collagen) densities from which extent of mineralization can be calculated non-invasively. This additional information has clinical implications for evaluating bone tissue in vivo in many diseases such as osteoporosis, healing of fractures and genetic disorders in children. Because the physiological and mechanical properties of bone are significantly dependent on the structure of the crystals, particularly the initial solid phase formed, studies will be pursued in situ by highly collimated synchrotron-generated wide-angle x-ray diffraction and simultaneous x-ray fluorescence (Ca concentration), FTIR imaging and microspectroscopy, and inelastic neutron scattering. We will also address the problem both theoretically and experimentally of the pre-nucleation states, viz., the chemical and structural conformation of the initial small clusters of Ca and P atoms and ions that are first bound to organic matrix constituents using molecular orbital calculations. Bone substance is a multiphase composite formed by the incorporation of brittle Ca-P nanocrystals into a soft organic matrix. Mechanical and physiological properties are also profoundly dependent on chemical and spatial relationships between the two major structural and other organic components, which will be studied by high-resolution synchrotron-generated low-angle x-ray diffraction providing the basis for mathematical modeling of spatial relationships between crystals and collagen and the spaces within the collagen fibril where the crystals are deposited. This will be accompanied -by the determination of the 3-dimensional shape and size of the crystals, determined by a new atomic force microscopy technique. Studies will continue on isolation, purification, and sequencing of phosphoproteins and sites of phosphorylation. Long-range goal wilt be preparation of single crystals of major species for crystallographic determination of molecular structure.

描述（由申请人提供）：生物无机晶体的功能取决于其大小、形状、长程和短程有序、化学成分、特定离子环境以及与细胞外基质和细胞的空间和化学关系。 骨功能包括对机械特性的贡献、维持细胞外液稳态的离子库以及与细胞的相互作用，所有这些都控制它们的相互作用特性，从而控制它们的机械和生理作用。 来自活体动物（最终是人类）的体外31 P NMR、光谱学和成像以及体内实验的数据将提供真实的3-D体积骨矿物质和骨基质（胶原）密度，由此可以非侵入性地计算矿化程度。 这些额外的信息对评估许多疾病（如骨质疏松症、骨折愈合和儿童遗传性疾病）体内骨组织具有临床意义。 由于骨的生理和机械性能显着依赖于晶体的结构，特别是形成的初始固相，研究将在原位进行高度准直同步加速器产生的广角X射线衍射和同步X射线荧光（钙浓度），FTIR成像和显微光谱，和非弹性中子散射。 我们还将从理论和实验两方面讨论预成核态的问题，即，使用分子轨道计算，首先与有机基质成分结合的Ca和P原子和离子的初始小簇的化学和结构构象。 骨物质是一种多相复合材料，由脆性的Ca-P纳米晶体掺入到软质有机基质中形成。 机械和生理特性也深刻地依赖于两个主要结构和其他有机成分之间的化学和空间关系，这将通过高分辨率同步加速器产生的低角度X射线衍射进行研究，为晶体和胶原蛋白之间的空间关系以及晶体沉积的胶原蛋白原纤维内的空间的数学建模提供基础。 这将伴随着-通过一种新的原子力显微镜技术确定晶体的三维形状和尺寸。 研究将继续对磷蛋白和磷酸化位点的分离，纯化和测序。 长期目标将是制备主要物种的单晶，用于分子结构的晶体学测定。