Immunohistochemical Analysis of Several Proteolytic Enzymes as Parameters of Cartilage Degradation

Abstract

Osteoarthritis is the most common joint disease in humans. It is characterized by a gradual loss of extracellular matrix components of articular cartilage such as collagen and proteoglycan. Presently, however, emphasis is placed on enzymes exerting a strong influence on cartilage degradation. These enzymes include matrix metalloproteinases (MMP), their specific inhibitors (TIMP) and the plasminogen activator/inhibitor system. We applied monoclonal antibodies against MMP-1, -2, -3, -9 and their inhibitors TIMP-1/-2, as well as against urokinase-plasminogen activator u-PA and its inhibitor PAI to investigate their influence on articular cartilage degradation in patients with varusgonarthritis. We examined the cartilage of the lateral and medial compartments of 20 tibia plateaus, which can present with slight and severe cartilage degradations at the same time. In doing so, we tried to show whether or not immunohistological detection of enzymes could serve as a parameter for chondral degradation. The strongest immunoreaction for all enzymes was noted in the superficial layer of articular cartilage both medially and laterally. Between medial and lateral compartments, however, there were striking differences in the immunoreaction intensity of chondrocytes for MMP-1 and -3 as well as for TIMP-1 and u-PA. We noted that in cartilage with more advanced degradation, the immunoreaction for these enzymes was significantly higher in medial than in lateral compartments (p < 0.05). At the immunohistological level, a direct correlation between the grade of cartilage degradation and immunoreaction intensity was found. Our results corroborate the assumption that the expression of certain matrix-degradating enzymes serves as a parameter for the grade of cartilage degradation.