BIOCHEMISTRY OF THE INTERVERTEBRAL DISC

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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.