Nature of Bone Mineral: Inception, Maturation, Aging

骨矿物质的性质：起始、成熟、老化

• 批准号: 6917241
• 负责人: MELVIN J GLIMCHER
• 金额: $ 49.22万
• 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/6917241
• 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它们的大小，形状，长距离和短距离顺序，化学成分，特定的离子环境以及与细胞外矩阵和细胞的空间和化学关系。 骨功能包括对机械特征的贡献，维持额外细胞液体体内稳态的离子储层以及与细胞的相互作用，所有这些都控制其交互性能，从而控制其机械和生理作用。 来自体外31p NMR的数据，光谱和成像以及活动物中的体内实验（最终人类）将提供真正的3-D体积骨矿物质和骨基质（胶原蛋白）密度，从中可以非侵入性地计算矿化程度。 这些附加信息对评估骨质疏松症，骨折治愈和儿童遗传疾病等许多疾病的体内骨组织具有临床意义。 由于骨骼的生理和机械特性显着取决于晶体的结构，尤其是形成的初始固相，因此将通过高度准确的同步器生成的广角X射线X射线衍射和同时X射线液体（CA浓度）（CA浓度），FTIR和微光谱成像和微光谱片段和散射效应。 我们还将在理论上和实验上解决核前态的问题，即CA和P原子和离子的初始小簇的化学和结构构象，这些簇首先使用分子轨道计算与有机基质成分结合。 骨骼物质是通过将脆性Ca-P纳米晶体掺入软有机基质中形成的多相复合材料。 机械和生理特性也深远取决于两个主要的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器生成的低角度X射线衍射来研究，这为晶体和胶原纤维之间的空间关系的数学建模提供了数学模型，其中晶体是晶体纤维中的。 通过确定由新的原子力显微镜技术确定的晶体的3维形状和尺寸，这将伴随着。 研究将继续进行磷酸化磷酸化蛋白和位点的分离，纯化和测序。 远程目标是制备主要物种的单晶，以确定分子结构的晶体学。