权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Chemical Structure Effects on Bone Response to Mechanical Load

化学结构对骨骼对机械负荷反应的影响

基本信息

批准号：
8661709
负责人：
MICHAEL DAVID MORRIS
金额：
$ 31.99万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8661709
关键词：
Age Aging Amino Acids Binding Biomechanics Biopsy Bone Diseases Bone Matrix Bone Tissue Calcium Calcium Carbonate Carbonates Cell Nucleus Cells Chemical Structure Chemicals Collagen Collagen Diseases Competence Complex Cross-Sectional Studies Deuterium Deuterium Oxide Development Exercise Failure Fatigue Fracture Genetic Glycine Goals Health Hydrogen Bonding Imaging Techniques Ions Location Magic Measurement Measures Mechanical Stress Mechanics Metabolic Diseases Minerals Modeling Molecular Conformation Movement Mus Mutation NMR Spectroscopy Nuclear Magnetic Resonance Osteoporosis Phenotype Physiologic pulse Population Porosity Positioning Attribute Proline Property Proteins Protocols documentation Protons Quantitative Trait Loci Research Personnel Resolution Role Secondary Protein Structure Series Site Specimen Stress Structure Surface Testing Time Tissues Uncertainty Water Water Movements Work age related behavior change biophysical techniques bone bone quality carboapatite crosslink disorder control inorganic phosphate method development mouse model new therapeutic target novel diagnostics research study response solid state solid state nuclear magnetic resonance tibia tool

项目摘要

DESCRIPTION (provided by applicant): We will apply solid-state magic angle spinning nuclear magnetic resonance spectroscopy (MAS-NMR) to measure changes in the chemical structure of bone tissue under mechanical load. MAS-NMR will allow us to examine ultrastructure contributions to bone quality that have, to date, been unobtainable using traditional imaging techniques or other biophysical techniques. The enabling advance is a special NMR cell that allows compressive loading and displacement measurements. High-resolution structural information will be correlated to strain of bone tissue from mature murine tibiae as the specimens are deformed under uniaxial compression. In Aim 1 we will assess distortion of the bone mineral lattice as changes in the mineral ion spacings and water mobility using a several different 1D and 2D solid-state NMR pulse sequences. We will also study load- induced changes in a series of synthesized carbonated apatites, which are model compounds for bone mineral to guide interpretation of our bone mineral results and to enable measurements with isotopically enriched nuclei, especially 43Ca. In these simplified model compounds we can accurately measure inter-ion distances, movement of mineral impurities, and reorganization of local symmetry and resolve uncertainties in the measurements of the more complex biomineral. In Aim 2 we will investigate the role of water in stabilizing both the mineral and matrix components via hydrogen bonding and enthalpic stabilization. Changes in collagen secondary structure will be measured through 13C resonances. We will use a unique protocol for controlled disordering of the collagen and mineral by partial and complete displacement of native matrix water with deuterium oxide, which forms weaker hydrogen bonds. NMR will probe water bridges and glycine-proline bonds, as well as mineral changes, with correlations to measured strain and applied load. In Aim 3 we will examine the loading response of mineral deformation, collagen conformation changes and hydrogen bonding in native and damaged bone tissue from mice of various ages in order to understand how age-related changes in the mineral and matrix compromise the mechanical competence of bone tissue. Controlled partial replacement of hydrogen ion with deuterium ion will be used to provide a range of collagen conformation changes.

描述(申请人提供)：我们将应用固态魔角旋转核磁共振波谱(MAS-核磁共振)来测量在机械载荷下骨组织化学结构的变化。MAS-核磁共振将使我们能够检查超微结构对骨骼质量的影响，这是到目前为止使用传统成像技术或其他生物物理技术无法获得的。实现这一进步的是一种特殊的核磁共振池，它允许测量压缩载荷和位移。当标本在单轴压缩下变形时，高分辨率结构信息将与来自成熟小鼠胫骨的骨组织的应变相关。在目标1中，我们将使用几种不同的一维和二维固态核磁共振脉冲序列来评估骨矿物晶格的扭曲，即矿物离子间距和水流动性的变化。我们还将研究一系列合成碳化磷灰石的负荷诱导变化，这些磷灰石是骨矿物的模型化合物，以指导我们的骨矿物结果的解释，并使同位素浓缩的核，特别是43Ca的测量成为可能。在这些简化的模型化合物中，我们可以准确地测量离子间距离、矿物杂质的移动和局部对称性的重组，并解决更复杂的生物矿物测量中的不确定因素。在目标2中，我们将通过氢键和焓稳定来研究水在稳定矿物和基质成分方面的作用。胶原蛋白二级结构的变化将通过13C共振进行测量。我们将使用一种独特的方案来控制胶原蛋白和矿物质的无序，方法是用氧化氢部分和完全置换天然基质水，这会形成较弱的氢键。核磁共振将探测水桥和甘氨酸-脯氨酸键，以及矿物变化，与测量的应变和施加的载荷相关。在目标3中，我们将检测不同年龄的小鼠天然和受损骨组织中矿物质变形、胶原构象变化和氢键的负荷响应，以了解与年龄相关的矿物质和基质的变化如何影响骨组织的机械能力。氢离子的受控部分置换将被用来提供一系列的胶原构象变化。