OSTEOARTHRITIC LESIONS - INVOLVEMENT OF 3 DIFFERENT COLLAGENASES

Objective. To assess the presence of fibroblast collagenase (MMP-1), n eutrophil collagenase (MMP-8), and collagenase 3 (MMP-13) in osteoarth ritic (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 w ere expressed at higher levels by OA chondrocytes than by normal chond rocytes, In addition, mRNA for MMP-8 was present in OA cartilage but n ot normal cartilage by PCR and Northern blot analyses, Chondrocytes fr om areas surrounding the OA lesion expressed greater quantities of MMP -1 and MMP-13 compared with normal chondrocytes, suggesting local modu lation by mechanical and inflammatory factors, Tumor necrosis factor a lpha stimulated the expression of all 3 collagenases. Retinoic acid, a n agent which induces autodigestion of cartilage in vitro, stimulated only the expression of MMP-13. Conclusion. These findings suggest a ke y role of MMP-13 and MMP-8, as well as MMP-1 in osteoarthritis.