Changes in aggrecan populations in experimental osteoarthritis

Adult articular cartilage contains at least two distinct populations of aggrecan: one is larger and richer in chondroitin sulfate (CS), while the other is smaller with less CS. The smaller form is thought to be derived from the larger. The amount of CS in cartilage decreases with maturation and aging, mainly because of a decrease in the proportion of the larger of these two proteoglycans. In early osteoarthritis (OA) the amount and concentration of CS in cartilage increases. To test the hypothesis that an increase in the more CS-rich form of aggrecan contributes to the increase in CS in cartilage in OA, experimental OA was induced in dogs by transection of the anterior cruciate ligament, with sacrifice at various times between 2 days and 64 weeks after the operation. Proteoglycans were extracted from the articular cartilage of eight areas of the joint, fractionated, and CS was quantified by measuring hexuronate. Aggrecan populations were assessed by composite agarose-polyacrylamide gel electrophoresis. The proportion of the more CS-rich form of aggrecan increased with time after operation in all areas of the joint. This increase correlated with increases in tissue mass and hexuronate, showing that the increase in the larger, CS-rich form of aggrecan contributes to the increase in CS in the tissue. It seems paradoxical that this form of aggrecan accumulates in the tissue despite the fact that increased protease activity has been demonstrated in experimental OA.