Autocrine induction of gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) and GLS-induced expression of matrix metalloproteinases in rheumatoid arthritis synoviocytes.
OBJECTIVE
The purpose of this study was to examine how gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) is involved in the molecular mechanism of cartilage degradation in rheumatoid arthritis (RA) with special reference to the GLS-induced gene expression and protein synthesis of matrix metalloproteinase (MMP)-1 (collagenase-1) and MMP-3 (stromelysin-1).


METHODS
Fibroblast-like synoviocytes (FLSs) obtained from RA patients were cultured and stimulated by GLS. Changes in the expression levels of GLS, MMP-1 and MMP-3 were assessed by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) for GLS, and by RT-PCR and enzyme-linked immunosorbent assay for MMPs and tissue inhibitor of metalloproteinase 1.


RESULTS
GLS demonstrated a self-induction of mRNA in cultured RA FLSs. GLS evoked a dose-dependent induction of MMP-1 and MMP-3 mRNAs, and subsequently their extracellular secretion.


CONCLUSIONS
These findings suggest that GLS is a plausible pathogenic factor causing the extensive joint destruction in RA mediated via MMPs.
Muro
H
H
Department of Orthopaedic Surgery and Department of Bioregulation Research, Nagoya City University Medical School, Nagoya 467-8601, Japan.
Waguri-Nagaya
Y
Y
Mukofujiwara
Y
Y
Iwahashi
T
T
Otsuka
T
T
Matsui
N
N
Moriyama
A
A
Asai
K
K
Kato
T
T
D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000378:metabolism*; D019898:Autocrine Communication; D004790:Enzyme Induction; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000201:enzymology / Q000378:metabolism*; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013939:Thymidine Phosphorylase; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1