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 tibia1 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. Address reprint requests to J. p. Pelletier, MD, Unit6 des Maladies Rhumatismales, HGpital Notre-Dame, 1560 rue Sherbrooke Est, Montreal, Quebec, Canada H2L 4K8.vised form November 11, 1986. tent (1). Recent reports by Sachs et a1 (2) and Goldberg et (3) describe types Of changes in metachromatic staining. Type A is characterized by a lack of perkellular staining, so that a halo appearance is present around the lacunae. The remainder Of the intertenitorial matrix has norma] metachromatic staining. The

Intraarticular Injections with Methylprednisolone Acetate Reduce Osteoarthritic Lesions in Parallel with Chondrocyte Stromelysin Synthesis in Experimental Osteoarthritis

“…Two specimens were dissected from the weight-bearing surfaces of each femoral condyle and tibial plateau, fixed in 10% buffered formalin, decalcified in 5% trichloroacetic acid solution for 48 hours, and embedded in paraffin for histologic study. Serial 6-pm sections (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) for each block) were prepared from the entire thickness of the block and stained with Safranin 0 or hematoxylin and eosin. The severity of the OA cartilage lesions was evaluated using the histologic/histochemical scale of Mankin et al (14).…”

“…Most of these studies were performed in vitro, and very little is known about the in vivo effect of corticosteroids on enzyme synthesis. Reports have indicated that steroids may possibly reduce stromelysin synthesis in situ (12).…”

Pharmacologic and Non-Pharmacologic Treatment of Osteoarthritis

“…Glucocorticoids have shown anti-inflammatory effects [64] and can inhibit the production of the collagenases that mediate cartilage damage in OA [65,66]. Intraarticular glucocorticoids can be used in OA, especially in patients who are not improved with NSAIDs treatment.…”

Aetiological Factors of Osteoarthritis: A Review Update

“…For example, a fracture through the joint surface often causes OA in joints in which the disease is otherwise rare such as the ankle and the wrist. Avascular necrosis can lead to collapse of dead bone at the articular surface, producing anatomic irregularities and subsequent OA [38][39][40] . Tears of ligaments that protect the joints, such as the anterior cruciate ligament in the knee and the labrum in the hip, can increase joint susceptibility and lead to premature OA.…”