MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis.
OBJECTIVE
To analyse matrix metalloproteinases (MMPs) and tissue inhibitor-1 of MMPs (TIMP-1) levels in the systemic circulation and synovial fluid (SF) of patients with RA and to compare these levels with inflammatory and collagen degradation markers.


METHODS
ProMMP-1, -2, -3, -8, -9, TIMP-1, levels of MMP/alpha(2)-macroglobulin complexes, and collagen degradation products were measured by sandwich ELISA, activity assays, and HPLC in paired SF and serum samples from 15 patients with RA and 13 with OA.


RESULTS
MMPs were higher in SF of patients with RA than in OA or controls. MMP levels in SF of patients with OA were higher than in controls. In serum, levels of proMMP-3, -8 and -9 were higher in patients with RA than in OA or controls, whereas only proMMP-8 and -9 were higher in serum of patients with OA than in controls. A strong correlation was seen between serum and SF levels of MMP-8 and -9 in RA. Increased levels of MMP/alpha(2)-macroglobulin complexes indicated an MMP/TIMP imbalance in serum and SF in RA. SF hydroxyproline correlated significantly with SF levels of proMMP-9 in RA.


CONCLUSIONS
Systemic MMP-8 and -9 levels represent the situation in the inflamed joint; MMP-9 is likely to be involved in degradation of joint collagen. The hypothesis of MMP/TIMP imbalance in RA is strengthened.
Tchetverikov
I
I
TNO Prevention and Health, PO Box 2215, 2301 CE, Leiden, The Netherlands.
Ronday
H K
HK
Van El
B
B
Kiers
G H
GH
Verzijl
N
N
TeKoppele
J M
JM
Huizinga
T W J
TW
DeGroot
J
J
Hanemaaijer
R
R
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D016022:Case-Control Studies; D017364:Collagenases / Q000097:blood; D004792:Enzyme Precursors / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000032:analysis / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000097:blood; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000097:blood*; D008666:Metalloendopeptidases / Q000097:blood; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000201:enzymology; D018709:Statistics, Nonparametric; D013582:Synovial Fluid / Q000201:enzymology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000097:blood; D000511:alpha-Macroglobulins / Q000032:analysis
D004792:Enzyme Precursors; D019715:Tissue Inhibitor of Metalloproteinase-1; D000511:alpha-Macroglobulins; D017364:Collagenases; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; C120487:pro-matrix metalloproteinase 9; C048047:prostromelysin; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D006909:Hydroxyproline