Determination of stromelysin-1, 72 and 92 kDa type IV collagenase, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in synovial fluid and serum from patients with rheumatoid arthritis.
OBJECTIVE
To investigate the correlation between serum and synovial fluid (SF) concentrations of stromelysin-1 (MMP-3), gelatinases (MMP-2 and MMP-9), tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in patients with rheumatoid arthritis (RA) and to assess the role of these proteins in cartilage destruction and their clinical value as indicators of disease activity.


METHODS
Enzyme linked immunoassays (ELISA) were used. SF and serum samples were collected simultaneously from 55 patients with RA. Radiographic (Larsen grade) and clinical evaluations were also done.


RESULTS
There was significant correlation between SF concentrations of MMP-3 and MMP-9. In addition, there was significant negative correlation between SF concentrations of TIMP-2 and MMP-2, 3, and 9. The only correlation observed among MMP and TIMP in serum was that of MMP-3 with MMP-2. Significant correlation was also found between MMP-3 concentrations in the serum and SF. There were no significant correlations between radiological grade and concentrations of these proteins. Patients with mild to moderate functional disability showed significantly higher serum TIMP-1 concentrations than patients with severe disability.


CONCLUSIONS
Extremely high concentrations of MMP-3 in SF of the patients with RA may contribute to its elevation in serum. It would seem that regulation of TIMP production depends upon the disease state and not the concentration of MMP. Discrepancies between concentrations of TIMP and MMP in SF may be responsible for cartilage destruction in RA.
Ishiguro
N
N
Department of Orthopedic Surgery, Nagoya University, School of Medicine, Japan.
Ito
T
T
Obata
K
K
Fujimoto
N
N
Iwata
H
H
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism*; D001769:Blood / Q000378:metabolism*; D017364:Collagenases / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9; D008875:Middle Aged; D008970:Molecular Weight; D009994:Osmolar Concentration; D011480:Protease Inhibitors / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D011480:Protease Inhibitors; D011506:Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9