Autocrine induction of gliostatin/platelet-derived endothelial cell growthfactor (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 mo lecular mechanism of cartilage degradation in rheumatoid arthritis (RA) wit h special reference to the GLS-induced gene expression and protein synthesi s of matrix metalloproteinase (MMP)-1 (collagenase-1) and MMP-3 (stromelysi n-1). Methods. Fibroblast-like synoviocytes (FLSs) obtained from RA patients were cultured and stimulated by GLS. Changes in the expression levels of GLS, M MP-1 and MMP-3 were assessed by Northern blot analysis and reverse transcri ption-polymerase chain reaction (RT-PCR) for GLS, and by RT-PCR and enzyme- linked immunosorbent assay for MMPs and tissue inhibitor of metalloproteina se 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 subsequent ly their extracellular secretion. Conclusion. These findings suggest that GLS is a plausible pathogenic facto r causing the extensive joint destruction in RA mediated via MMPs.