Proteoglycan‐degrading acid metalloprotease activity in human osteoarthritic cartilage, and the effect of intraarticular steroid injections

Abstract

Cartilage samples from both the immediate and remote lesion areas were obtained from the tibial plateaus of 21 patients with osteoarthritis, and were subjected to histologic and enzymatic study. There was a frequent loss of pericellular metachromatic staining in the OA cartilage. Seven patients had received intraarticular injections of steroids, and in 21% of those cartilage samples, a pericellular halo was seen. This halo was seen in 71% of patients who had not received steroid injections. The total acid metalloprotease activity was increased more than twofold in specimens from OA lesions and in those samples graded moderate, as compared with age‐matched control cartilages. These differences were greater when the specimens from patients who had received steroid therapy were excluded from the data. The cartilage specimens from steroid‐treated patients were not significantly different from those of controls with respect to the enzyme activity in the lesions or in cartilage with moderate disease. The active form of the protease was suppressed by steroids. In samples from patients who did not receive steroid injections and who had a moderate grade of OA, a significantly elevated level of the active protease was present, as compared with control samples. Those samples graded moderate which came from patients who received steroid treatments showed no difference in the active protease level versus that of controls. Our results are consistent with the hypothesis that acid metalloprotease activity is involved in the degradation of the cartilage matrix in OA. Since the protease retains a significant fraction (40%) of its activity at neutral pH, its physiologic role might occur either at acid pH or at neutral pH. The halo surrounding the chondrocytes (the result of a local loss of proteoglycan) might be related to the action of this enzyme. Preliminary evidence has suggested that steroids reduce cartilage enzyme activity.