COLLAGENS OF CARTILAGE AND THE INTERVERTEBRAL DISC

这个项目正在使用蛋白质化学的先进方法来理解 各种分子的聚合物结构和相互作用 构成软骨和椎间骨架的胶原蛋白类型 盘状组织。长期目标是定义各种类型的 胶原蛋白在基质中有组织，它们在多大程度上 被设计为自组装并相互之间以及与其他 形成杂聚纤维的基质大分子 网络。在矩阵体系结构中需要分子差异 不同形式的软骨以及单个区域内的不同区域 组织，包括与邻近非软骨组织的连接结构域 组织，以及不同胶原蛋白化学和修饰的作用 分子尤其令人感兴趣。两种组织，关节软骨 和间盘，将用牛进行最详细的研究 和人力资源。一个焦点话题是分子间的共价方式。 交联度与异型聚合的范围 胶原蛋白分子的亚家族。具体目标包括定义 准确地说，共价相互作用的分子位置和化学 在II型和II型胶原之间，研究交叉感染的发生率 I型和II型胶原蛋白之间的连接，定义了交联性 胶原蛋白V/XI亚家族链异构型的相互作用机制 基因产物，了解基质分解素和其他 细胞外蛋白水解酶在降解软骨胶原网络中的作用 发现X型胶原蛋白的交联性机制。最新的 蛋白质化学的技术将是主要的方法，包括 高效液相多肽分离，气相自动氨基酸测序， 专门的方法来检测和定量独特的胶原交叉- 连接氨基酸，并使用特定抗体。 这项工作的临床意义在于提供了一种分子基础 了解关节软骨退化的过程 在骨关节炎关节(骨关节炎)和椎间盘断裂 随着成年年龄的增加而下降，并导致常见的脊柱疾病 (腰背痛)。在这两种组织中，胶原骨架的失败是 软骨组织退变的一个不可逆的中心特征。 有理由相信，组织可能存在共同的机制 关节软骨和关节盘的破坏。

This project is using advanced methods in protein chemistry to understand the polymeric architecture and interactions of the various molecular types of collagen that form the framework of cartilage and intervertebral disc tissue. The long-term objective is to define how the various kinds of collagenous protein are organized in the matrix, to what degree they are designed to self-assemble and interact with each other and with other matrix macromolecules in order to form the heteropolymeric fibrillar network. The need for molecular differences in the matrix architecture of different forms of cartilage and between regions within a single tissue, including junction domains with adjacent non-cartilaginous tissues, and the role of different collagen chemistries and modifying molecules are of particular interest. Two tissues, articular cartilage and intervertebral disc, will be studied in greatest detail using bovine and human sources. A focal topic is the manner of covalent intermolecular cross-linking and the scope of heterotypic polymerization in and between the collagen sub-families of molecules. Specific aims include defining precisely the molecular sites and chemistry of covalent interaction between types IX and II collagens, studying the incidence of cross- linking between types I and II collagens, defining the cross-linking mechanisms among the chain isotypes of the collagen V/XI sub-family of gene products, understanding the action of stromelysin and other extracellular proteases in degrading the cartilage collagen network and discovering the mechanism of cross-linking in type X collagen. The latest techniques in protein chemistry will be the primary approach, including HPLC peptide separations, gas-phase automated amino acid sequencing, specialized methods to detect and quantify the unique collagen cross- linking amino acids, and use of specific antibodies. The clinical significance of this work is in providing a molecular basis for understanding the processes whereby articular cartilage is degraded in osteoarthritic joints (osteoarthritis) and intervertebral discs break down with increasing adult age and contribute to common spinal disorders (low back pain). In both tissues a failure of the collagen framework is a central irreversible feature of the cartilage tissue degeneration. There is reason to believe that there may be common mechanisms of tissue destruction in joint cartilages and discs.