OSTEOPOROSIS, COLLAGEN CROSS-LINKS & BIOMECHANICS

描述(申请人提供)：在研究矿物变化期间 骨质疏松骨的特性，明显改变了骨的质量 有机基质作为同一个体内解剖位置的函数 被观察到了。这项提议的总体目标是检验这样一个假设 骨质疏松患者的有机基质有一致的变化 与正常相比，正常依赖于解剖位置，并应 胶原蛋白性质的差异。这将通过 调查三个具体目标： 目的1：检验假设存在显著差异 正常和骨质疏松人类骨骼之间的胶合/基质特性。 此外，这些差异在活跃的骨形成中也是明显的 表面。这一假说将通过与髂骨的比较来解决。 确诊为骨质疏松症的患者的活组织检查 组织学/组织形态计量学参数，非 骨质疏松症的形态测量证据。这些研究将以组织学为基础， 和FTIR成像(FTIRI)技术。目标2：检验假设 观察到的差异是生化特性变化的函数 胶原蛋白，主要是交联型(程度、成熟度、来源)。这 将通过一系列生化和FTIR分析的比较来验证 高纯度的胶原蛋白多肽。另外。量化的问题 将获得描述胶原交联物的光谱参数 利用成熟的化学方法来修饰前牙本质。目标3：测试 认为骨骼的力学性能的变化是依赖于 部分是关于有机基质的质量。这一目标将记录 傅立叶变换红外光电子能谱观察力学模型中胶原-交联型的变化 在一个有充分记录的动物模型系统中研究骨骼的特性。散装胶原蛋白 质量将通过化学方法和几何/解剖变化进行分析 由FTIRI提供。这些研究将使用来自 胶原蛋白/结构已知的β-氨基丁腈大鼠动物模型 将被修改，其几何和结构属性都将 下定决心。 拟议的研究将基于组织学、FTIR成像(FTIRI)、 生物力学和生化技术，代表了一种新的方法 骨质疏松中有机基质的评价。

DESCRIPTION (provided by applicant): During studies of the variation in mineral properties in osteoporotic bone, an apparent alteration in the quality of the organic matrix as a function of anatomical location within the same individual was observed. The overall goal of this proposal is to test the hypothesis that there are consistent alterations in the organic matrix of osteoporotic patients compared with normals, which are dependent on the anatomical site, and are due to differences in collagen properties. This will be accomplished through the investigation of three specific aims: Aim 1: To test the hypothesis that there are significant differences in collage/matrix properties between normal and osteoporotic human bones. Furthermore, that these differences are evident in actively bone forming surfaces. This hypothesis will be addressed by comparison of iliac crest biopsies from individuals in whom osteoporosis has been determined based on histologic/histomorphometric parameters, with biopsies from those without morphometric evidence of osteopenia. These studies will be based on histology, and FTIR Imaging (FTIRI) techniques. Aim 2: To test the hypothesis that the observed differences are a function of variations in the biochemical properties of collagen, primarily cross-linking pattern (extent, maturity, origin). This will be verified by a comparison of biochemical and FTIR analyses of a series of highly purified collagen peptides. Additionally. quantitation of the spectroscopic parameters describing collagen cross-links will be achieved utilizing well-established chemical methods to modify predentin. Aim 3: To test the hypothesis that variation in the mechanical properties of bone is dependent part on the quality of the organic matrix. This aim will document the effect of changes in collagen-cross linking pattern observed by FTIRI on the mechanical properties of bone in a well-documented animal model system. Bulk collagen quality will be analyzed by chemical means, and geometric/anatomical variations by FTIRI. These studies will be performed using bones from the beta-aminoproprionitrile rat animal model in which collagen/structure is known to be modified, and for which both geometric and structural properties will be determined. The proposed studies will be based on histology, FTIR Imaging (FTIRI), biomechanical, and biochemical techniques and represent a novel approach to evaluating the organic matrix inosteoporosis.