Comparison of the catabolic effects of fibronectin fragments in human knee and ankle cartilages

Objective: To compare the response of knee and ankle cartilages to fibronectin fragments (Fn-f) in terms of kinetics of matrix proteoglycan (PG) degradation and synthesis, since previous data had shown that knee was more sensitive to Fn-f in terms of steady-state PG content. Design: Human knee and ankle cartilage explants were treated with the 29 kDa Fn-f, and its effects on PG-degradation kinetics, on the half-lives of S-35-sulfate-labeled PG, on PG synthesis suppression and on matrix metalloproteinase -3 (MMP-3) were compared. Cultures were also treated with the interleukin (IL) receptor antagonist protein (IRAP) in order to determine whether IL-1 is involved in the Fn-f effect. Results: The Fn-f enhanced PG-degradation rates in both human knee and ankle cartilages. Knee cartilage showed a greater effect of Fn-f on half-lives of newly synthesized S-35-labeled PG than ankle. The extent of release of MMP-3 was similar for human ankle and knee cartilages. However, PG synthesis in knee cartilage was sensitive to 10- to 100-fold lower concentrations of Fn-f than was ankle cartilage. IRAP partially reversed Fn-f activity in ankle cartilages. Conclusions: The role of Fn-f in proteolysis leading to cartilage damage appears to be minor in human cartilages than had previously been shown for bovine. This decreased proteolysis is true for both knee and ankle. The major difference between human ankle and knee cartilage appears to be greater sensitivity to PG synthesis suppression in knee cartilage. A further indication that IL-1 is involved in the pathway was provided by the partial reversal with IRAP. (C) 2003 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.