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Rheumatology Advance Access originally published online on January 20, 2004
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Rheumatology 2004; 43: 448-452
Rheumatology Vol. 43 No. 4 (c) British Society for Rheumatology 2004; all rights reserved

Basic Science

Cytokines regulate fibroblast-like synovial cell differentiation to adipocyte-like cells

S. Yamasaki, T. Nakashima1, A. Kawakami, T. Miyashita, F. Tanaka, H. Ida, K. Migita, T. Origuchi and K. Eguchi

First Department of Internal Medicine and 1Department of Oncology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan

Correspondence to: K. Eguchi. E-mail: eguchi{at}net.nagasaki-u.ac.jp

Objectives. Our recent work showed that fibroblast-like synovial cells (FLS) could differentiate into adipocyte-like cells in vitro in response to stimulation with peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) ligand. The aim of the present study was to determine the role of cytokines in the regulation of FLS differentiation to adipocyte-like cells.

Methods. FLS isolated from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and from normal synovial tissues were incubated with the synthetic PPAR{gamma} ligand troglitazone to induce adipocyte-like differentiation of the cells.

Results. Production of interleukin (IL)-6, IL-8 and matrix metalloproteinase-3 was reduced in adipocyte-like cells compared with FLS. DNA binding activity of nuclear factor {kappa}B (NF-{kappa}B) was clearly inhibited in adipocyte-like cells. Cultivation of FLS with interferon {gamma} (IFN-{gamma}), tumour necrosis factor-{alpha} (TNF-{alpha}) or IL-1ß inhibited the expression of PPAR{gamma} as well as CCAAT/enhancer binding protein (C/EBP) nuclear activity, and thus suppressed adipocyte-like cell differentiation in vitro.

Conclusion. Our results indicate the importance of PPAR{gamma} and C/EBP in adipocyte-like cell differentiation of FLS and that the process is influenced by inflammatory cytokines, and suggest that the proinflammatory character of FLS in patients with RA is diminished during adipocyte-like cell differentiation.

KEY WORDS: Adipogenesis, Cytokines, NF-{kappa}B, PPAR{gamma}, CCAAT/enhancer binding protein.


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