Autocrine induction of gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) and GLS-induced expression of matrix metalloproteinases in rheumatoid arthritis synoviocytes

• Published in: Rheumatology (Oxford, England) Vol. 38; no. 12; pp. 1195 - 1202
• Main Authors: Muro, H., Waguri-Nagaya, Y., Mukofujiwara, Y., Iwahashi, T., Otsuka, T., Matsui, N., Moriyama, A., Asai, K., Kato, T.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.1999; Oxford Publishing Limited (England)
• Subjects: Arthritis, Rheumatoid - enzymology; Arthritis, Rheumatoid - metabolism; Autocrine Communication; Biological and medical sciences; Diseases of the osteoarticular system; Enzyme Induction; Gliostatin; Humans; In Vitro Techniques; Inflammatory joint diseases; Interleukin-1 - metabolism; Matrix metalloproteinase; Matrix Metalloproteinase 1 - biosynthesis; Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 3 - biosynthesis; Matrix Metalloproteinase 3 - metabolism; Medical sciences; Platelet-derived endothelial cell growth factor; Reverse Transcriptase Polymerase Chain Reaction; Rheumatoid arthritis; RNA, Messenger - metabolism; Synovial Membrane - enzymology; Synovial Membrane - metabolism; Thymidine phosphorylase; Thymidine Phosphorylase - metabolism; Tumor Necrosis Factor-alpha - metabolism; Human; Immunopathology; Synovitis; Endothelial cell; Stromelysin 1; Enzyme; Pathogenesis; Diseases of the osteoarticular system; Autoimmune disease; Metalloendopeptidases; Inflammatory joint disease; Inflammation; Degradation; Peptidases; Chronic; Articular cartilage; Rheumatoid arthritis; Hydrolases; Molecular biology; ELISA assay; Platelet derived growth factor; Interstitial collagenase
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/38.12.1195

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. Conclusion. These findings suggest that GLS is a plausible pathogenic factor causing the extensive joint destruction in RA mediated via MMPs.