Fibronectin fragments cause chondrolysis of bovine articular cartilage slices in culture

Elevated fibronectin (Fn) and Fn fragment concentrations are found in the synovial fluid of osteoarthritic and rheumatoid arthritic patients. Fn has been shown to affect expression of chondrocytic matrix proteins, and Fn fragments have been shown to elevate gene expression of neutral proteinases in...

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Bibliographic Details
Published in:The Journal of biological chemistry 1992-02, Vol.267 (6), p.3597-3604
Main Authors: HOMANDBERG, GA, MEYERS, R, XIE, DL
Format: Article
Language:English
Subjects:
Animals
Biochemistry & Molecular Biology
Biological and medical sciences
Cartilage, Articular - drug effects
Cartilage, Articular - enzymology
Cartilage, Articular - metabolism
Cattle
Culture Techniques
Diseases of the osteoarticular system
Endopeptidases - metabolism
Fibronectins - pharmacology
Hydrolysis
Kinetics
Life Sciences & Biomedicine
Medical sciences
Osteoarthritis
Proteoglycans - metabolism
Science & Technology
Synovial Fluid - metabolism
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Summary:Elevated fibronectin (Fn) and Fn fragment concentrations are found in the synovial fluid of osteoarthritic and rheumatoid arthritic patients. Fn has been shown to affect expression of chondrocytic matrix proteins, and Fn fragments have been shown to elevate gene expression of neutral proteinases in synoviocytes. For these reasons, we tested the effects of Fn fragments on protease release and resultant proteoglycan release from cartilage in serum-free bovine articular cartilage explant cultures. We have found that 1 microM amino-terminal 29- and 50-kDa gelatin-binding Fn fragments caused over a 50-fold enhancement of gelatinolytic and collagenolytic proteinase release with a 23-fold enhancement of proteoglycan (PG) release. Release was significant at fragment concentrations as low as 20 nM. An integrin-binding 140-kDa fragment mixture was the least active fragment, whereas native Fn had little activity. The relative activities of the fragments correlated with their relative abilities to bind to cartilage. The RGDS integrin-recognition peptide also caused release, although sequence mutants did not. PG release was blocked by actinomycin D, cycloheximide, and deoxyglucose. Fn fragment-mediated PG release was decreased in 10% serum by over 10-fold but was still 2-fold greater than in controls. In the presence of insulin-like growth factor-1, PG release was as great as without serum. We suggest that Fn fragments, as found in diseased synovial fluid, may contribute to protease-mediated damage to cartilage.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(19)50566-X