Matrix Metalloproteinase 3 and Joint Destruction in Rheumatoid Arthritis

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Matrix Metalloproteinase 3 and Joint Destruction in Rheumatoid Arthritis

S. Fauci

[Copyright © 1998, 1999, 2000 by The McGraw-Hill Companies, Inc. Reproduced with

permission of The McGraw-Hill Companies.]

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Matrix Metalloproteinase 3 (MMP-3) is a proteinase that plays an important role

in cartilage degradation; its substrates include aggrecan core protein,

cartilage link protein, fibronectin, and a variety of types of collagen.

Overexpression of MMP-3 has been demonstrated in rheumatoid synovium, and

synovial fluid from patients with rheumatoid arthritis (RA) contains high levels

of MMP-3. Analysis of proteoglycan core fragments in synovial fluid from RA

patients reveals proteolytic cleavage at a site consistent with cleavage by

MMP-3. In light of these data, Yamanaka and colleagues (2000) studied a possible

association between MMP-3 levels in serum and subsequent joint destruction in

patients with RA.

The study group included 267 normal healthy controls and 82 patients with RA; 26

of these RA patients had early RA, with <1 year of polyarthritis, and 56

patients had chronic RA of >5 years duration. Serum MMP-3 levels were

significantly higher in patients with RA compared with normal controls (239 vs.

41 ng/mL). There was no significant difference in these levels when patients

with early and chronic RA were compared. In both groups of patients with RA,

inflammatory markers, such as the erythrocyte sedimentation rate and C-reactive

protein levels, were correlated with MMP-3 levels. MMP-3 levels were

significantly associated with a radiologic measure of joint destruction in

patients with chronic, but not early, RA. Of note, the MMP-3 levels in patients

with early RA did correlate with radiologic measures of joint destruction 6 and

12 months after entry into the study. Furthermore, increases in MMP-3 levels

over the first 12 months of follow-up in these early RA patients correlated with

measures of joint destruction at 12-24 months after entry into the study. Thus,

MMP-3 levels served as a strong predictor of the subsequent clinical course of

RA in these patients.

These data strongly suggest the predictive value of serum MMP-3 levels with

regard to subsequent joint destruction in early RA. Serum MMP-3 levels also

correlated with classic inflammatory markers and with the degree of joint

destruction in chronic RA. A role for MMP-3 in the pathogenesis of RA is

suggested by these and other data, forming the rationale for choosing MMP-3 as a

possible target of therapeutic intervention.

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