COLLAGENASE-1 AND COLLAGENASE-3 SYNTHESIS IN NORMAL AND EARLY EXPERIMENTAL OSTEOARTHRITIC CANINE CARTILAGE - AN IMMUNOHISTOCHEMICAL STUDY

Objective. The coexistence of different collagenases in cartilage sugg ests the possibility of specific roles for these enzymes in the degrad ation of the collagen network in osteoarthritis (OA). We investigated the in situ synthesis and distribution of collagenase-1 and collegenas e-3 in normal and early experimental OA cartilage. Methods. The OA mod el was created on 12 mongrel dogs by sectioning the anterior cruciate ligament of the right stifle joint with a stab wound. Dogs were divide d into 3 groups of 4 animals each, and sacrificed at 4, 8, and 12 week s, respectively. A 4th group (n = 4) of unoperated dogs was used as co ntrol. Articular cartilage from femoral condyles and tibial plateaus w as examined histologically to grade severity of lesions, and immunohis tochemical and morphometric analyses were performed to detect the pres ence of chondrocytes producing collagenase-1 and -3. Results. In OA do gs, the histologic severity of lesions increased with time, being most severe at 8 and 12 weeks after surgery. In cartilage from OA compared to unoperated dogs, the immunoreactivity was 5-9 times higher (p < 0. 0002) for collagenase-1, and 3-6 times higher (p < 0.0002) for collage nase-3, in both femoral condyles and tibial plateaus. Although the cel l score increased throughout the cartilage, comparison of the superfic ial and upper intermediate layers (superficial) with the lower interme diate and deep layers (deep) revealed a significantly higher level for collagenase-1 (p < 0.007) in the superficial layers, contrary to the collagenase-3 data, which indicated a higher level (p < 0.007) in the deep layers. For collagenase-1, the cell score increased steadily up t o the 12th week, and for collagenase-3, the elevation peaked at 8 week s. Correlation between the histologic severity and cell score in carti lage specimens from unoperated and OA dogs revealed the highest coeffi cient for collagenase-1 at the superficial layers (r = 0.69, p < 0.000 1), while for collagenase-3, this was noted at the deep layers (r = 0. 65, p < 0.0004). Conclusion. The number of chondrocytes involved in th e synthesis of collagenase-1 and collegenase-3 increases dramatically in the early phase of OA. However, the difference in the topographic d istribution of these enzymes, as well as the variation in their correl ation pattern, may reflect a different function allocated for each col lagenase in the OA cartilage degradation process.