Irreversible Changes in Glycosaminoglycan Composition of Anatomically Intact Bovine Articular Cartilage Induced by Intermittent Loading

Abstract

The changes in matrix composition induced by I MPa intermittent (0.2 Hz) loading of anatomically intact bovine articular cartilage in vitro are studied. The kinetics of chondrocyte response was determined in experiments where sesamoid bones of adult cows were loaded for 0, 3, 5 and 7 days. The reversibility of the induced changes were studied in sesamoid bones that were loaded for 5 days and subsequently cultured without loading for another 1, 2 and 3 weeks. Water content was not affected by loading, nor by subsequent unloaded culture. Glycosaminoglycan content was not affected by loading, nor by subsequent unloaded culture for another 2 weeks. However, after 3 weeks of culture following 5 days of loading, a significant decrease in glycosaminoglycan content was found. Glycosaminoglycan synthesis was already increased after 3 days of loading. Loading for longer periods (5 and 7 days) further increased the glycosaminoglycan synthesis rate. Glycosaminoglycan synthesis decreased during the first week of subsequent culture without loading. In the third week it dropped to a lower level than observed for the control. The amount of 3-B-3(-) epitope was increased and the length of newly synthesized glycosaminoglycans was decreased by intermittent loading. Subsequent unloaded culture did not further increase the amount of 3-B-3(-) epitope. However, after 3 weeks of unloaded culture the newly synthesized glycosaminoglycans were as long as those synthesized in the control. The results suggest that the changes in glycosaminoglycan chain length were reversible. However, the overall chondrocyte response to our loading regime seems to be detrimental to the tissue: expression of 3-B-3(-) epitope induced by loading together with the drop in glycosaminoglycan content and synthesis observed at the end of the total culture period indicate that the cartilage is irreversibly damaged.