[MMP- and FAP-mediated non-inflammation-related destruction of cartilage and bone in rheumatoid arthritis]

Due to morphological similarities of high-grade synovitis in rheumatoid Arthritis (RA) and mesenchymal, semimalignant tumors and the hypothesis that RA progression is not only inflammation-related, but also determined by tumor-like mechanisms, a comparison was made between expression profiles of RA, giant cell tumor of bone (GCT) and normal synovium (ND).

Array data of selected genes were validated through immunohistochemical staining of paraffin-embedded and deep frozen tissue samples of GCT, RA and normal synovium.

With microarray analysis, CCR1, CCR5, MMP-1, MMP-2, MMP-3, MMP-9, MMP-14 and FAP were found to be significantly upregulated in RA and GCT compared to ND. A significant upregulation in RA and GCT compared to ND could be validated by immunohistochemistry for MMP-1, MMP-9, MMP-14 and FAP.

For MMPs, and MMP-9 in particular, an important role in early cartilage destruction of RA was suggested. The presence of FAP in RA and in stroma of a semimalignant tumor indicates tumor-like tissue destruction in chronic synovitis associated with RA.