Rheumatology Advance Access originally published online on November 22, 2005
Rheumatology 2006 45(4):421-424; doi:10.1093/rheumatology/kei209
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Monocyte chemoattractant protein-4 (MCP-4)/CCL13 is highly expressed in cartilage from patients with rheumatoid arthritis
1 Institute of Rheumatology, Tokyo Women's Medical University, 2 Department of Orthopaedic Surgery, School of Medicine, Keio University and 3 Institute for Drug Discovery, Yamanouchi Pharmaceutical Co., Ltd, Tberaki, Japan.
Correspondence to: H. Okamoto, Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku, Tokyo 162-0054, Japan. E-mail: hokamoto{at}ior.twmu.ac.jp
Objectives. To study the role of monocyte chemoattractant protein-4 (MCP-4)/CCL13 in the pathogenesis of rheumatoid arthritis (RA), we analysed the expression of MCP-4/CCL13 in chondrocytes, synovial fluid and serum from patients with RA and investigated the effect of MCP-4/CCL13 on the proliferation of synovial cells.
Methods. Human articular cartilage specimens were obtained from joints from RA and osteoarthritis (OA) patients and normal joints (controls). Transcript levels of MCP-4 in cartilage were determined by real-time polymerase chain reaction. Protein levels were measured by enzyme-linked immunoassay. Cultured fibroblast-like synoviocytes (FLS) were treated with various concentrations of recombinant MCP-4/CCL13 protein, and cell proliferation was evaluated with a viability assay.
Results. The gene expression of MCP-4 was significantly higher in cartilage from RA patients than in that from OA patients (P = 0.00902) and in normal cartilage (P = 0.00902). The concentration of MCP-4/CCL13 protein in serum from RA patients (mean 94.7 ± 37.6 pg/ml) was significantly higher than in serum from OA patients (mean 49.2 ± 31.2 pg/ml, P = 0.0051) and controls (mean 32.6 ± 23.9 pg/ml, P = 0.0001). The concentration of MCP-4/CCL13 protein in synovial fluid from RA patients (mean 247.2 ± 161.2 pg/ml) was also significantly higher than in that from OA patients (mean 29.6 ± 50.5 pg/ml, P = 0.000019). Moreover, MCP-4/CCL13 enhanced the proliferation of FLS in a dose-dependent manner.
Conclusions. MCP-4/CCL13 is highly expressed in RA joints at the mRNA and protein levels. Our results suggest that MCP-4/CCL13 is secreted from chondrocytes and activates the proliferation of rheumatoid synovial cells, thereby leading to joint destruction in RA.
KEY WORDS: Rheumatoid arthritis, Monocyte chemoattractant protein-4, Chemokines