Serum levels of collagenase, stromelysin-1, and TIMP-1. Age- and sex-related differences in normal subjects and relationship to the extent of joint involvement and serum levels of antigenic keratan sulfate in patients with osteoarthritis.
OBJECTIVE
To measure serum levels of collagenase (MMP-1), stromelysin-1 (MMP-3), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in normal subjects and in patients with osteoarthritis (OA), and to assess how these correlate with biochemical and clinical indicators of disease activity in OA.


METHODS
Specific immunoassays were used to measure MMPs, TIMP-1, and antigenic keratan sulfate (KS). The total area of cartilage affected by the disease was measured (expressed as an articular index).


RESULTS
In the normal population (n = 118), the serum concentration of MMP-3, but not of MMP-1 or TIMP-1, increased with age and was approximately 2 times higher in males than in females. In the OA patients (n = 33), the serum levels of MMP-3, but not of MMP-1 or TIMP-1, were significantly elevated and correlated strongly with the articular index but poorly with objective and subjective functional capacity scores as well as with serum levels of antigenic KS and systemic parameters of inflammation.


CONCLUSIONS
These findings illustrate the importance of matching patients and normal controls for age and sex in further studies of MMP-3 and are consistent with the hypothesis that MMP-3 might play an important role in the degradation of joint cartilage in OA. Further, serum levels of MMP-3 may prove useful for monitoring therapy for OA.
Manicourt
D H
DH
Saint Luc University Hospital, University of Louvain, Brussels, Belgium.
Fujimoto
N
N
Obata
K
K
Thonar
E J
EJ
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000941:Antigens / Q000097:blood; D001799:Blood Sedimentation; D017364:Collagenases / Q000097:blood*; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007632:Keratan Sulfate / Q000276:immunology; D008297:Male; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000097:blood*; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood* / Q000188:drug therapy; D019714:Tissue Inhibitor of Metalloproteinases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D007632:Keratan Sulfate; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3