Induction of collagenase-3 (MMP-13) in rheumatoid arthritis synovial fibroblasts

There is a growing body of evidence that implicates matrix metalloproteinas es (MMPs) as major players in numerous diseased conditions. The articular c artilage degradation that is characteristic of rheumatoid arthritis (RA) is believed to be mediated by the collagenase subfamily of matrix metalloprot einases. The preference of collagenase-3 (CL-3) for collagen type II makes it a likely candidate in the turnover of articular cartilage and a potentia l target for drug development.]In this study, RA synovial membrane tissue w as shown to express CL-3 mRNA by reverse transcriptase-polymerase chain rea ction (RT-PCR) and protein by immunohistochemistry. Fibroblasts isolated an d cultured from RA synovial membrane tissue were induced to express CL-3 mR NA. CL-3 mRNA was detected after PMA treatment in 16 of the 18 RA synovial membrane fibroblast cell lines established for this study. These fibroblast s also expressed mRNA for collagenase-1 (CL-1, MMP-1), membrane type-1 matr ix metalloproteinase, gelatinase A, gelatinase B, stromelysin-l, stromelysi n-2, TIMP-1, and TIMP-2. They were further shown to express CL-1 mRNA const itutively and CL-3 mRNA only after stimulation with PMA, IL-1, TGF-beta1, T NF-alpha, or IL-6 with IL-6sR. These fibroblasts also expressed after induc tion both CL-1 and CL-3 at the protein level as determined by Western blot analyses and immunofluorescence. (C) 2000 Elsevier Science B.V. All rights reserved.