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Arthritis Rheum. 2001 Nov;44(11):2503-11.

Relationships of matrix metalloproteinases and their inhibitors to cartilage proteoglycan and collagen turnover and inflammation as revealed by analyses of synovial fluids from patients with rheumatoid arthritis.

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1
Department of Orthopaedic Surgery, Nagoya University, School of Medicine, Japan. j46163a@nucc.cc.nagoya-u.ac.jp

Abstract

OBJECTIVE:

To determine interrelationships in matrix turnover in articular cartilage and joint inflammation in rheumatoid arthritis (RA).

METHODS:

Synovial fluid was obtained from the knees of 63 RA patients; radiographs were evaluated to determine the RA stage. Concentrations of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), the 846 epitope, and the keratan sulfate (KS) epitope of aggrecan, the C-propeptide of cartilage type II procollagen (CPII; biosynthetic marker), the cleavage of type II collagen by collagenase (CIIC; generated neoepitope), and polymorphonuclear leukocyte elastase (PMNE; inflammation marker) were measured by immunoassay. Concentrations of the unsaturated disaccharides of hyaluronic acid (delta di-HA) and the proteoglycan glycosaminoglycan disaccharides of chondroitins 4 and 6 sulfate (delta di-C4S and delta di-C6S) were determined by high-performance liquid chromatography.

RESULTS:

MMP-3 was markedly increased in RA compared with osteoarthritis. Increases in TIMP-1 in RA were less pronounced and were inversely correlated with MMP-3 levels. CIIC was reduced in RA, as was the release of the KS epitope and delta di-C6S. In contrast, delta di-C4S and the 846 epitope were up-regulated. PMNE levels correlated with the 846 epitope and delta di-C4S, and more strongly with TIMPs 1 and 2. The changes may signify attempts at control of proteolysis in parallel with increased aggrecan turnover, which would favor matrix assembly. PMNE also correlated with MMP-9, and MMP-9 correlated with CPII. The delta di-HA level was decreased in RA and was inversely correlated with CPII and MMP-9 as well as with MMPs 2 and 3. In contrast, delta di-HA was directly correlated with TIMP-1 and the 846 epitope. These observations suggest that HA and PMNs may be involved in the control of proteolysis and cartilage proteoglycan assembly.

CONCLUSION:

Our observations provide new insights into the complex changes in cartilage turnover and PMN influx in RA joints.

[Indexed for MEDLINE]
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