Osteoarthritic Lesions. Involvement of three different collagenases

Objective. To assess the presence of fibroblast collagenase (MMP‐1), neutrophil collagenase (MMP‐8), and collagenase 3 (MMP‐13) in osteoarthritic (OA) cartilage, with particular emphasis on areas of macroscopic cartilage erosion. Methods. Messenger RNA (mRNA) levels were assessed by reverse transcriptase‐polymerase chain reaction (RT‐PCR), in situ hybridization, and Northern blot analysis. Results. MMP‐1 and MMP‐13 were expressed at higher levels by OA chondrocytes than by normal chondrocytes. In addition, mRNA for MMP‐8 was present in OA cartilage but not normal cartilage by PCR and Northern blot analyses. Chondrocytes from areas surrounding the OA lesion expressed greater quantities of MMP‐1 and MMP‐13 compared with normal chondrocytes, suggesting local modulation by mechanical and inflammatory factors. Tumor necrosis factor α stimulated the expression of all 3 collagenases. Retinoic acid, an agent which induces autodigestion of cartilage in vitro, stimulated only the expression of MMP‐13. Conclusion. These findings suggest a key role of MMP‐13 and MMP‐8, as well as MMP‐1 in osteoarthritis.