Muro H, Waguri-Nagaya Y, Mukofujiwara Y, Iwahashi T, Otsuka T, Matsui N, Moriyama A, Asai K, Kato T
Department of Orthopaedic Surgery and Department of Bioregulation Research, Nagoya City University Medical School, Nagoya 467-8601, Japan.
Rheumatology (Oxford). 1999 Dec;38(12):1195-202. doi: 10.1093/rheumatology/38.12.1195.
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).
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.
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.
These findings suggest that GLS is a plausible pathogenic factor causing the extensive joint destruction in RA mediated via MMPs.
本研究旨在探讨胶质抑素/血小板衍生内皮细胞生长因子（GLS/PD-ECGF）如何参与类风湿关节炎（RA）中软骨降解的分子机制，特别关注GLS诱导的基质金属蛋白酶（MMP）-1（胶原酶-1）和MMP-3（基质溶解素-1）的基因表达及蛋白质合成。
培养从RA患者获取的成纤维样滑膜细胞（FLS），并用GLS刺激。通过Northern印迹分析和针对GLS的逆转录-聚合酶链反应（RT-PCR），以及针对MMP和金属蛋白酶组织抑制剂1的RT-PCR和酶联免疫吸附测定，评估GLS、MMP-1和MMP-3表达水平的变化。
GLS在培养的RA FLS中显示出mRNA的自我诱导。GLS引起MMP-1和MMP-3 mRNA的剂量依赖性诱导，随后是它们的细胞外分泌。
这些发现表明，GLS是通过MMP介导导致RA中广泛关节破坏的一个可能的致病因素。
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