The uronic acid (proteoglycan, PG) content of cartilage from habitually unloaded sites of normal canine femoral condyles has been shown to be lower than that from habitually loaded regions, even though the glycosaminoglycan (GAG) synthesis is similar. We investigated whether the GAG degradation in unloaded cartilage would be greater than that in loaded cartilage, and we obtained comparative biochemical data concerning the PGs and organization of the extracellular matrix of noi-ma1 loaded and unloaded cartilage. PG extractability (qetermined by sequential guanidinium chloride extracts of cartilage), percentage of PGs forming large aggregates, and hydrodynamic size of the PG monomers (determined by Sepharose 2B chromatography) were essentially the same in loaded and unloaded cartilage. As expected, the uronic acid content of unloaded cartilage was 20% lower than that of loaded cartilage (P < 0.02), while the water and DNA contents of the 2 tissues were not statistically different. There was no difference in the rate of net "S04-GAG synthesis in organ cultures of loaded and unloaded cartilage. Moreover, there was no appreciable difference in the rates of "S04-GAG degradation of loaded and unloaded cartilage, ais determined by "SO4 pulse-chase studies. We have previously shown that selective cyclic compressive stresses applied in vitro to cartilage from loaded areas of canine femoral condyles may increase "S04-GAG synthesis. The present results suggest that the rates of GAG metabolism in loaded and unloaded cartilage under atmospheric pressure in vitro may not reflect the rates which exist in articular joints under compressive loads in vivo.A number of reports have suggested that a causal relationship exists between the proteoglycan (PG) content of connective tissue and the mechanical stress to which it is subjected. Thus, the glycosaminoglycan (GAG) content of load-bearing areas of dermis (l), articular cartilage (2-5), and tendon (6,7) is greater than that of habitually unloaded areas of the same tissues. Furthermore, it is clear that such differences can be modulated in vivo (8,9). An increase in compressive loading of the normal canine shoulder has been shown to produce an in vivo increase in the chondroitin sulfate content of the articular cartilage of the humeral head (9). Conversely, when loading of articular cartilage is reduced, e.g., by immobilization of the ipsilateral limb, net PG synthesis (8,lO) is decreased and the glycosaminoglycan content (1 1
GAG IN LOADED AND UNLOADED CARTILAGE
89either increased or decreased net GAG biosynthesis, depending on the duration of loading (18).In preliminary studies, we found that the level of net GAG synthesis in normal canine femoral condylar cartilage from habitually loaded areas was comparable with that in cartilage from habitually unloaded areas of the same joint (4). Since the uronic acid content of cartilage from unloaded sites is lower than that of cartilage from loaded regions, we hypothesized that the rate of GAG degradation in unloaded cartilage would be g...