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


CONCLUSIONS
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.
Yamasaki
S
S
First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Nakashima
T
T
Kawakami
A
A
Miyashita
T
T
Tanaka
F
F
Ida
H
H
Migita
K
K
Origuchi
T
T
Eguchi
K
K
D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D016207:Cytokines / Q000502:physiology*; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D010003:Osteoarthritis / Q000473:pathology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology*; D045162:Thiazolidinediones / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D000077288:Troglitazone
D002839:Chromans; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D019278:Matrix Metalloproteinase 3; D000077288:Troglitazone