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Rheumatology Advance Access published online on January 20, 2004
Rheumatology, doi:10.1093/rheumatology/keh092
Rheumatology © British Society for Rheumatology 2004; all rights reserved
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© 2004 Rheumatology © British Society for Rheumatology 2004; all rights reserved

Original Papers

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

S. Yamasaki 1, T. Nakashima 2, A. Kawakami 1, T. Miyashita 1, F. Tanaka 3, H. Ida 1, K. Migita 1, T. Origuchi 1, and K. Eguchi 1*

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

* Corresponding author. E-mail: eguchi{at}net.nagasaki-u.ac.jp.

Received 21 June 2003 ; revised 6 November 2003

Abstract

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-1{beta} 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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