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 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.
Homandberg
G A
GA
Department of Biochemistry, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3864.
Meyers
R
R
Xie
D L
DL
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002417:Cattle; D046508:Culture Techniques; D010450:Endopeptidases / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology*; D006868:Hydrolysis; D007700:Kinetics; D011509:Proteoglycans / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism
D005353:Fibronectins; D011509:Proteoglycans; D010450:Endopeptidases