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


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


RESULTS
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.


CONCLUSIONS
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.
Jakobs
M
M
Zentrum für Histologie, Zytologie und Molekulare Diagnostik Trier, Trier, Deutschland.
Häupl
T
T
Krenn
V
V
Guenther
R
R
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D001842:Bone and Bones / Q000276:immunology*; D002356:Cartilage / Q000276:immunology*; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000032:analysis*; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis*; D008565:Membrane Proteins / Q000032:analysis*; D054388:Receptors, CCR / Q000032:analysis*; D012697:Serine Endopeptidases / Q000032:analysis*; D000099167:Fibroblast Activation Protein Alpha
D015415:Biomarkers; D010450:Endopeptidases; D018093:Gelatinases; D020782:Matrix Metalloproteinases; D008565:Membrane Proteins; D054388:Receptors, CCR; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha