BIOCHEMISTRY OF THE INTERVERTEBRAL DISC

软骨和软骨中不同分子类型的胶原 椎间盘是此次调查的重点。长的- 术语目标是对如何实现各种目标的基本理解 胶原蛋白分子在基质中聚合到什么程度 它们被设计成专门相互交互，并与 其他基质大分子并自组装成具有功能的 纤维状网络。特别有趣的是， 胶原蛋白中的共价分子间交联及其研究进展 异型聚合的潜力。目标包括定义 IX型和II型胶原的共价相互作用部位 分子，以及V型和I型与XI型和II型胶原之间 在椎间盘和其他骨骼组织中。这个 兔VI型胶原的分布、功能及其随年龄的变化 人体圆盘将被检查。一种新的胶原蛋白 我们将描述纤维环的特征，并探讨其功能。 蛋白质化学的最新技术将是主要的 方法，包括广泛使用高效液相多肽分离，气体- 阶段自动氨基酸测序和专门的方法 检测和定量独特的胶原蛋白交联型氨基酸。 各种胶原蛋白的合成速度将在#年确定。 体外培养的组织外植体。随着工作的进展，一个 还将努力研究分离的矩阵表达 原代高密度单层培养中的视盘细胞。 到35岁时，所有的人类腰椎间盘都显示出进行性退行性改变 一岁，许多专家认为这是一次重要的身体检查 腰背痛综合症背后的因素。主要特征是 这些变化包括分裂、裂缝、错位、失水和 其他局部破坏有组织的胶原蛋白框架的迹象 髓核和纤维环。中国的基础研究 这项提议的目的是提高对分子生物学的认识。 这个复杂的胶原蛋白框架是如何组装的，如何 细胞在成熟的组织中维持它，以及它在 退化。

The different molecular types of collagen in cartilage and intervertebral disc are the focus of the investigation. The long- term objective is a basic understanding of how the various kinds of collagen molecule are polymerized in the matrix, to what degree they are designed to interact specifically with each other and with other matrix macromolecules and self-assemble into a functioning fibrillar network. Of particular interest is the manner of covalent intermolecular cross-linking in collagens and the potential for heterotypic polymerization. Aims include defining the sites of covalent interaction between types IX and II collagen molecules, and between types V and I and types XI and II collagens in intervertebral disc and other skeletal tissues. The distribution, function and changes with age in type VI collagen of the human disc will be examined. A new collagenous protein of annulus fibrosus will be characterized and its function explored. The latest techniques in protein chemistry will be the primary approach, including extensive use of HPLC peptide separations, gas- phase automated amino acid sequencing and specialized methods to detect and quantify the unique collagen cross-linking amino acids. Rates of synthesis of the various collagens will be determined in tissue explants incubated in vitro. As the work progresses, an effort will also be made to study the matrix expression of isolated disc cells in primary high-density monolayer cultures. All human lumbar discs show progressive degenerative changes by 35 yr of age, which many experts believe is a significant physical factor behind the low back pain syndrome. The cardinal features of these changes are splits, fissures, dislocations, water loss and other signs of local damage to the organized collagen framework of the nucleus pulposus and annulus fibrosus. The basic studies in this proposal are aimed at an improved knowledge at the molecular level of how this complex collagen framework is assembled, how cells maintain it in the mature tissue and what happens to it in degeneration.