OSTEOARTHRITIS (OA) is a major cause of disability. The majority of clinically demonstrable secondary OA involves some compromise in joint stability. Rupture of the ANTERIOR CRUCIATE LIGAMENT (ACL) is a common SPORTS INJURY and OA frequently develops as a consequence. Elucidation of the early and late molecular and cellular mechanisms in cartilage degeneration following ACL rupture would provide information essential to the design of a rational approach towards the management of this and other types of OA. A characteristic feature of early OA is a disorganized fibrillar matrix, implicating a defect in intermolecular and cell-matrix adhesion molecules. Immunolocalization experiments suggest that the pericellular distribution of type VI collagen (COLL VI) is disorganized in OA. We here address the hypothesis that COLL VI is a pivotal intermolecular adhesion and cell attachment factor in the maintenance of tissue homeostasis. We hypothesize that it functions: (a) by interacting with other matrix molecules; (b) by functioning as a cell attachment factor for cartilage chondrocytes and meniscal fibrochondrocytes. This hypothesis will be addressed by isolating intact COLL VI and investigating its capacity to interact with cells and a variety of matrix macromolecules. These experiments will delineate the role of COLL VI in the maintenance of the integrity of the normal cartilage matrix.
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