Osteoarthritis (degenerative joint disease) is the most common form of arthritis. If occurs almost universally in the aged, and results in significant disability in over 20% of patients. Therapy at present is symptomatic rather than specific. Therapeutic intervention to prevent, retard or reverse the disease will depend upon increased knowledge of pathogenic and pathophysiologic factors involved in the disease process. Cartilage changes associated with aging processes must be differentiated from those characteristic of osteoarthritis. The availability of a reproducible experimental animal model of osteoarthritis developed in this laboratory, as well as use of well characterized in vitro organ culture techniques provide opportunity for more intensive investigation of disease mechanisms and directions for experimental therapeutic intervention. Studies utlizing an in vivo experimental model and in vitro culture techniques are designed to compare and contrast normal, aging and osteoarthritic cartilage with respect to 1) qualitative and quantitative metabolism of chondrocyte proteoglycan and collagen; 2) to delineate the role of proteolytic and collagenolytic enzymes; 3) to study the effects of estrogens and related hormonal compounds on cartilage; 4) to study cartilage prostaglandins as they related to enzymatic cartilage degradation, and to proteoglycan and collagen synthesis/repair processes; and 5) to define mechanisms of osteophyte formation. Investigations are directed towards the elucidation of further insights to osteoarthritis and therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR030134-08
Application #
3155755
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1981-12-01
Project End
1986-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
8
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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Mehraban, F; Kuo, S Y; Riera, H et al. (1994) Prostromelysin and procollagenase genes are differentially up-regulated in chondrocytes from the knees of rabbits with experimental osteoarthritis. Arthritis Rheum 37:1189-97
Moskowitz, R W; Reese, J H; Young, R G et al. (1991) The effects of Rumalon, a glycosaminoglycan peptide complex, in a partial meniscectomy model of osteoarthritis in rabbits. J Rheumatol 18:205-9
Moskowitz, R W; Boja, B; Denko, C W (1991) The role of growth factors in degenerative joint disorders. J Rheumatol Suppl 27:147-8
Denko, C W; Boja, B; Moskowitz, R W (1990) Growth promoting peptides in osteoarthritis: insulin, insulin-like growth factor-1, growth hormone. J Rheumatol 17:1217-21
Mehraban, F; Moskowitz, R W (1989) Serum keratan sulfate levels in rabbits with experimentally induced osteoarthritis. Arthritis Rheum 32:1293-9