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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR034614-02
Application #
3156881
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1984-12-01
Project End
1989-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Montefiore Medical Center (Bronx, NY)
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10467
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Bidanset, D J; LeBaron, R; Rosenberg, L et al. (1992) Regulation of cell substrate adhesion: effects of small galactosaminoglycan-containing proteoglycans. J Cell Biol 118:1523-31
Leroux, J Y; Poole, A R; Webber, C et al. (1992) Characterization of proteoglycan-reactive T cell lines and hybridomas from mice with proteoglycan-induced arthritis. J Immunol 148:2090-6
Bidanset, D J; Guidry, C; Rosenberg, L C et al. (1992) Binding of the proteoglycan decorin to collagen type VI. J Biol Chem 267:5250-6

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