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.
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.
Authors: Hong Seo Choi; Chun Jeih Ryu; Hyun Mi Choi; Jin Sung Park; Jae-Hoon Lee; Kang Il Kim; Hyung-In Yang; Myung Chul Yoo; Kyoung Soo Kim Journal: Mol Med Rep Date: 2012-01-25 Impact factor: 2.952