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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR039569-06
Application #
2079583
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1988-07-01
Project End
1996-04-30
Budget Start
1994-05-01
Budget End
1996-04-30
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Type
DUNS #
017730458
City
Cleveland
State
OH
Country
United States
Zip Code
44195
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Miller, R R; McDevitt, C A (1995) Thrombospondin 1 binds to the surface of bovine articular chondrocytes by a linear RGD-dependent mechanism. FEBS Lett 363:214-6
McDevitt, C A; Marcelino, J; Tucker, L (1991) Interaction of intact type VI collagen with hyaluronan. FEBS Lett 294:167-70
Miller, R R; McDevitt, C A (1991) A quantitative microwell assay for chondrocyte cell adhesion. Anal Biochem 192:380-3
Miller, R R; McDevitt, C A (1991) Thrombospondin in ligament, meniscus and intervertebral disc. Biochim Biophys Acta 1115:85-8
McDevitt, C A; Webber, R J (1990) The ultrastructure and biochemistry of meniscal cartilage. Clin Orthop Relat Res :8-18
McDevitt, C A; Miller, R R (1989) Biochemistry, cell biology, and immunology of osteoarthritis. Curr Opin Rheumatol 1:303-14