Fibronectin fragments bind to and penetrate cartilage tissue resulting in proteinase expression and cartilage damage.
We have reported that fibronectin (Fn) fragments added to bovine articular cartilage slices in culture causes marked cartilage damage by enhancing proteinase expression and resultant degradation and release of proteoglycan (PG). Several different non-overlapping Fn fragments, an amino-terminal 29-kDa, gelatin-binding 50-kDa and integrin-binding 140-kDa Fn fragment, representing nearly all of the polypeptide chain, were compared in terms of ability to cause PG release from cartilage and to bind cartilage. The most active fragment, the 29-kDa fragment, was able to enter cartilage in an intact metacarpophalangeal joint in culture and cause PG release at the same rate as with surgically cut cartilage. Further, when radiolabelled 29-kDa fragment was added to cartilage, a large proportion bound the intact articular surface, while a lesser amount diffused throughout the tissue matrix and concentrated in clusters near the mid-section of full thickness cartilage. The 29-kDa, 50-kDa, 140-kDa Fn fragments and Fn, respectively, showed PG degradation activities 9-, 6-, 2- and 1.1-fold that of control levels and bound cartilage to the extent of 180, 20, 18 and 2 pmol/100 mg cartilage, respectively. Therefore, the PG degradation activities were greatest for the smaller fragments, which bound to the greatest extent. The apparent Kd values for interaction of the 29-kDa, 50-kDa, 140-kDa fragments and Fn for cartilage tissue were about 1.2, 0.3, 0.1 and 0.02 microM, respectively, and the order was inversely related to PG degradation activities. We conclude that the smaller the Fn fragment, the greater the degradation activity and extent of binding to cartilage tissue, but the weaker the affinity.
Xie
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Department of Biochemistry, Rush Medical College, Rush-Presbyterian-St Luke's Medical Center, Chicago, IL 60612-3864.
Homandberg
G A
GA
D000818:Animals; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D005353:Fibronectins / Q000494:pharmacology*; D008662:Metacarpophalangeal Joint; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism
D005353:Fibronectins; D010446:Peptide Fragments; D011509:Proteoglycans