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

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 γ (PPARγ) 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 PPARγ 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 κB (NF-κB) was clearly inhibited in adipocyte-like cells. Cultivation of FLS with interferon γ (IFN-γ), tumour necrosis factor-α (TNF-α) or IL-1β inhibited the expression of PPARγ 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 PPARγ 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. © British Society for Rheumatology 2004; all rights reserved.