Pannus invasion and cartilage degradation in rheumatoid arthritis: involvement of MMP-3 and interleukin-1beta.
OBJECTIVE
Synovial inflammation in rheumatoid arthritis (RA) leads to pannus tissue invasion and destruction of cartilage/bone matrix by proteinases. Our intention was to analyze some of the key matrix metalloproteinases (MMPs) in pannus tissue overlying evolving cartilage erosions in RA.


METHODS
Frozen tissue samples of pannus and synovium from advanced RA and synovium from osteoarthritic patients were used for immunohistochemical, western blotting and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis of MMP-1, -3, -13 and -14. Synovial fibroblast cultures, stimulated with tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), were analyzed with enzyme-linked immunosorbent assays (ELISA) and quantitative RT-PCR.


RESULTS
MMP-3 was highly expressed in pannus tissue compared with significantly lower expression levels of MMP-1, -13 and -14. In fibroblast cultures IL-1beta was a potent stimulus for MMP-3, whereas TNF-alpha was more potent for MMP-1.


CONCLUSIONS
This is the first study to demonstrate quantitatively in real time that MMP-3 mRNA expression is clearly higher in advanced RA pannus tissue compared to parallel RA or osteoarthritic synovium. MMP-3 mRNA levels were also clearly overexpressed in RA pannus compared to MMP-1, -13 and -14. Advanced RA has previously been found to overexpress IL-1beta. The high expression of MMP-3 in pannus and IL-1beta, mediated stimulation of MMP-3 suggest that MMP-3 plays a significant role in the progression of erosions through the proteoglycan-rich cartilage matrix.
Ainola
M M
MM
Institute of Biomedicine, Department of Anatomy, University of Helsinki, Helsinki, Finland.
Mandelin
J A
JA
Liljeström
M P
MP
Li
T F
TF
Hukkanen
M V J
MV
Konttinen
Y T
YT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002357:Cartilage Diseases / Q000276:immunology*; D017364:Collagenases / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology*; D020781:Matrix Metalloproteinase 1 / Q000276:immunology; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000276:immunology*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000276:immunology; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology; D013585:Synovitis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1