Osteoarthritis (OA, degenerative joint disease) is the most common form of arthritis. It occurs almost universally in the aged, and results in significant disability in over 20% of patients. Although the etiology of OA is unknown, studies suggest etiologic roles for biochemical, chemical, inflammatory and immunologic factors. It has become increasingly evident that interplays of synovium, cartilage and bone contribute in significant fashion to primary and augmenting pathophysiologic processes. This proposal is designed to 1) use monoclonal antibodies to separately identify serum antigen or antibody markers which reflect cartilage (proteoglycans, glycosaminoglycans, type II collagen), or bone (type I collagen; bone derived CSA, cartilage-stimulating activity factor) so as to noninvasively study cartilage/bone changes in osteoarthritic, normal and aging joints in experimental models and in humans; 2) investigate sequential tissue changes in cartilage lesions in experimental OA using monoclonal antibodies which recognize specific epitopes on rabbit cartilage proteoglycans; and 3) determine the role of immune factors in augmentation of degradative and (secondary) inflammatory changes observed in experimental OA. The relationship of immunoglobulin deposition to evolving pathologic changes will be studied, and reactive antigenic determinants defined. Immunochemical responses of cartilage components to biomechanical, hormonal and biochemical manipulations will be investigated. Studies will provide insights in osteoarthritis pathophysiology and allow for advances in disease definition and diagnosis.
