Nitric oxide mediates interleukin-1-induced gene expression of matrix metalloproteinases and basic fibroblast growth factor in cultured rabbit articular chondrocytes

Kazuhiro Sasaki, Takako Hattori, Takuo Fujisawa, Kojiro Takahashi, Hajime Inoue, Masaharu Takigawa

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

We recently reported that nitric oxide (NO), which is produced by chondrocytes treated with interleukin-1β (IL-1), releases basic fibroblast growth factor (bFGF) stored in the matrix of articular chondrocytes. To clarify the mechanism of the IL-1-induced bFGF release, we investigated the production and gene expression of bFGF, matrix metalloproteinases (MMPs), syndecan 3, and inducible NO synthase (iNOS) by IL-1-treated rabbit articular chondrocytes. IL-1 stimulated not only the release of bFGF but also the production of it. Gelatin and casein zymography revealed that IL-1 stimulated the production of not only MMP-9 but also MMP-3. The increase in the production of these MMPs preceded the IL-1-stimulated bFGF release. An MMP inhibitor partially suppressed the release of bFGF, indicating that matrix degradation is at least partially involved in the IL-1-stimulated bFGF release even if increased production of bFGF is related to the release. IL-1 sequentially stimulated mRNA expression of iNOS, membrane type 1-MMP, MMP-9 and -3, and bFGF, in that order. N(G)-Monomethyl-L-arginine, an inhibitor of NO production, inhibited gene expression of MMP-9 and bFGF. These findings suggest that elevation of the NO level via iNOS mRNA expression stimulated by IL-1 mediates gene expression and production of MMPs and bFGF, resulting in the release of bFGF, and also reveal molecular mechanisms implicating the degradation of articular cartilage followed by angiogenesis in the synovium in arthritic joints.

Original languageEnglish
Pages (from-to)431-439
Number of pages9
JournalJournal of biochemistry
Volume123
Issue number3
DOIs
Publication statusPublished - Mar 1998

Keywords

  • Basic fibroblast growth factor
  • Chondrocytes
  • Interleukin-1β
  • Matrix metalloproteinase
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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