OSTEOPOROSIS, COLLAGEN CROSS-LINKS & BIOMECHANICS

描述（由申请人提供）：在研究矿物的变化期间 在骨质疏松症骨的性质，在质量的明显改变， 有机基质作为同一个体内解剖位置的函数 观察了本提案的总体目标是检验以下假设： 有一致的改变，在器官基质的病人， 与正常人相比，这取决于解剖部位， 胶原蛋白特性的差异。这将通过以下方式实现： 调查的三个具体目标： 目的1：检验以下假设： 胶原/基质性质之间的正常和骨质疏松的人骨。 此外，这些差异在活跃的骨形成中是明显的。 表面。这一假设将通过比较髂嵴 来自个体的活组织检查，在所述个体中，骨质疏松症已经基于 组织学/组织形态计量学参数，有来自无 骨质减少的形态学证据。这些研究将基于组织学， 和FTIR成像（FTIRI）技术。目的2：检验以下假设： 观察到的差异是生物化学性质变化的函数 胶原蛋白，主要是交联模式（程度，成熟度，来源）。这 将通过一系列生物化学和FTIR分析的比较进行验证 高纯度的胶原蛋白肽另外。的定量 将获得描述胶原交联的光谱参数 利用成熟的化学方法来修饰前牙本质。目标3：测试 骨的力学性质的变化取决于 有机基质的质量。这一目标将记录 通过FTIRI在机械上观察到的胶原交联模式的变化 骨的性质在一个有据可查的动物模型系统。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 通过FTIRI。这些研究将使用来自 已知胶原蛋白/结构的β-氨基丙腈大鼠动物模型 将被修改，并且其几何和结构特性将被 测定 拟定研究将基于组织学、FTIR成像（FTIRI）， 生物力学和生化技术，代表了一种新的方法， 评估骨质疏松症的有机基质。

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.