Determination of interstitial collagenase (MMP-1) in patients with rheumatoid arthritis.
OBJECTIVE
To investigate whether interstitial collagenase (MMP-1) concentration in synovial fluid can be useful as a marker for disease activity in rheumatoid arthritis (RA), to determine the main route by which collagenase degrades the matrix of articular cartilage, and to investigate if an imbalance between metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP) is responsible for the activity of MMPs in RA.


METHODS
Collagenase concentrations were measured in synovial fluid and paired serum samples using a specific sandwich enzyme linked immunosorbent assay. Collagenase activities were also assayed in synovial fluid samples. Synovial tissues obtained from the same patient were examined by immunohistochemical staining and the numbers of cells expressing collagenase were counted.


RESULTS
Collagenase concentrations in synovial fluid did not correlate with C reactive protein and collagenase levels in serum, but did correlate positively with the degree of synovial inflammation, and increased with increasing numbers of cells identified as expressing collagenase in synovial tissue. Collagenase activities did not correlate with TIMP-1 concentrations, but did correlate strongly with the ratios of collagenase concentration to TIMP-1 (r = 0.73).


CONCLUSIONS
The collagenase concentration in synovial fluid cannot be used as a marker for systemic disease activity, but can be used as a marker for the degree of synovial inflammation in the joint from which the sample is aspirated. In advanced RA, most of the collagenase is probably produced in synovial lining cells and released into synovial fluid, where it degrades the matrix of articular cartilage. An imbalance between MMP and TIMP may be of importance in the degradation of extracellular matrix of articular cartilage in RA.
Department of Orthopaedic Surgery, Tohoku University, School of Medicine, Sendai, Japan.
S
S
Maeda
T
T
Sawai
M
M
Uzuki
Y
Y
Takahashi
H
H
Omoto
M
M
Seki
M
M
Sakurai
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D015415:Biomarkers / Q000032:analysis; D017364:Collagenases / Q000032:analysis* / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000378:metabolism; D008875:Middle Aged; D013582:Synovial Fluid / Q000201:enzymology; D013583:Synovial Membrane / Q000201:enzymology*; D019714:Tissue Inhibitor of Metalloproteinases
D015415:Biomarkers; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D008666:Metalloendopeptidases; D020781:Matrix Metalloproteinase 1