Marked suppression by salicylate of the augmented proteoglycan synthesis in osteoarthritic cartilage

In osteoarthritis a net increase in proteoglycan synthesis has been noted until the disease is far advanced and presumably reflects an attempt by the chondrocyte to repair the defect in the cartilage matrix. Because salicylates are the agents most commonly employed in treatment of osteoarthritis and because we recently showed that 10(-3) M sodium salicylate (i.e., approximately 20 mg%) suppresses proteoglycan synthesis in normal canine knee cartilage in vitro, we have studied the effects of this compound on osteoarthritis knee cartilage from dogs whose anterior cruciate ligament had been transected 9 weeks previously. The data indicated that the augmented synthesis of glycosaminoglycans in the degenerating cartilage was suppressed to a much greater degree by 10(-3) M sodium salicylate than the lower level of glycosaminoglycan synthesis in control cartilage from the contralateral knee of the same animal. Uptake of 14C-acetylsalicylic acid was increased about 35% in osteoarthritic cartilage, suggesting that the drug permeated it more readily than normal cartilage. The salicylate-induced suppression of proteoglycan synthesis in the osteoarthritic cartilage was not accompanied by reversal of the defect in proteoglycan aggregation or by improvement in the (presumed) defect in proteoglycan-collagen interaction in the matrix, as reflected by the abnormally high proportion of 35S-proteoglycans present in the culture medium.