Pathobiology of Articular Cartilage Degeneration

Rosenberg, Lawrence

Abstract

The long term goal is to determine whether the partial substitution of dermatan sulfate proteoglycans (DS-PGs) of small size with feeble elastic properties for cartilage-specific proteoglycans of large size with potent elastic properties is a central event in the development of the articular cartilage degeneration which occurs in several human diseases. We have recently demonstrated the presence of DS-PGs in significant amounts in aging bovine articular cartilages. The articular cartilages contain two different species of DS-PGs called DS-PGI and DS-PGII, with molecular weights of 80,000 to 140,000. DS-PGI self-associates, while DS-PGII does not.
The specific aims of the proposed research are: to develop efficient methods for the isolation to homogeneity of DS-PGI and DS-PGII, to prepare DS-PGI and DS-PGII from bovine and human articular cartilages in amounts sufficient for detailed chemical studies and to prepare monospecific antibodies to each species; to define the structure and properties of the two proteoglycans in terms of chemical composition, molecular weights and self-association properties; to show that DS-PGI and DS-PGII possess different core proteins; to elucidate the basis for the self-association of DS-PGI, in terms of the copolymeric structure of its glycosminoglycan chains; to determine the changes in the concentrations of the DS-PGs which occur during aging in bovine and human articular cartilages; to determine whether the partial substitution of DS-PGs for cartilage-specific proteoglycans during aging predisposes and contributes to the development of osteoarthritis, and to determine whether this phenomenon is involved in the pathogenesis of osteoarthritis.