IMMUNOHISTOCHEMICAL ANALYSIS OF SEVERAL PROTEOLYTIC-ENZYMES AS PARAMETERS OF CARTILAGE DEGRADATION

Osteoarthritis is the most common joint disease in humans. It is chara cterized by a gradual loss of extracellular matrix components of artic ular 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), t heir specific inhibitors (TIMP) and the plasminogen activator/inhibito r system. We applied monoclonal antibodies against MMP-, 1, -2, -3, -9 and their inhibitors TIMP-1/-2, as well as against urokinase-plasmino gen activator u-PA and its inhibitor PAI to investigate their influenc e on articular cartilage degradation in patients with varusgonarthriti s. 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 parame ter for chondral degradation. The strongest immunoreaction for all enz ymes was noted in the superficial layer of articular cartilage both me dially and laterally. Between medial and lateral compartments, however , there were striking differences in the immunoreaction intensity of c hondrocytes 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 f or these enzymes was significantly higher in medial than in lateral co mpartments (p < 0.05). At the immunohistological level, a direct corre lation between the grade of cartilage degradation and immunoreaction i ntensity was found. Our results corroborate the assumption that the ex pression of certain matrix-degradating enzymes serves as a parameter f or the grade of cartilage degradation.