Nitric oxide mediates interleukin-1-induced matrix degradation and basic fibroblast growth factor release in cultured rabbit articular chondrocytes: A possible mechanism of pathological neovascularization in arthritis

Tomoo Tamura, Tohru Nakanishi, Yusuke Kimura, Takako Hattori, Kazuhiro Sasaki, Hiromichi Norimatsu, Kojiro Takahashi, Masaharu Takigawa

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Prolonged incubation with interleukin-1β (IL-1) induced the release of large amounts of NO and subsequently inhibited DNA synthesis and the biosynthesis and accumulation of proteoglycans in cultured rabbit articular chondrocytes (RAC). IL-1 also inhibited DNA synthesis in bovine aortic endothelial cells (BAE). On the other hand, DNA synthesis in BAE cocultured with RAC was not inhibited by prolonged incubation with IL-1. Moreover, conditioned media from RAC incubated for a long period with IL-1 stimulated DNA synthesis in BAE alone. This growth stimulatory activity was mainly due to the release of basic fibroblast growth factor, a heparin-binding growth factor, into RAC culture. Gelatin zymography of the RAC culture medium revealed that IL-1 increased the production of matrix met alloproteinase-2 (MMP-2) and MMP-9. N(G)-Monomethyl-L-arginine, an inhibitor of NO synthesis, inhibited all of these actions of IL-1. These results indicate that NO from RAC treated with IL-1 stimulates MMPs, which, in turn, degrade the extracellular matrix produced by RAC, resulting in the release of large amounts of basic fibroblast growth factor stored in the matrix, which then stimulates adjacent BAE proliferation. Thus, NO produced from RAC treated with IL-1 may modulate angiogenesis in the synovium of arthritic patients.

Original languageEnglish
Pages (from-to)3729-3737
Number of pages9
JournalEndocrinology
Volume137
Issue number9
DOIs
Publication statusPublished - 1996

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Pathologic Neovascularization
Fibroblast Growth Factor 2
Chondrocytes
Interleukin-1
Arthritis
Nitric Oxide
Joints
Rabbits
Endothelial Cells
DNA
Matrix Metalloproteinases
Synovial Membrane
Proteoglycans
Gelatin
Conditioned Culture Medium
Extracellular Matrix
Culture Media
Arginine
Heparin
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Nitric oxide mediates interleukin-1-induced matrix degradation and basic fibroblast growth factor release in cultured rabbit articular chondrocytes : A possible mechanism of pathological neovascularization in arthritis. / Tamura, Tomoo; Nakanishi, Tohru; Kimura, Yusuke; Hattori, Takako; Sasaki, Kazuhiro; Norimatsu, Hiromichi; Takahashi, Kojiro; Takigawa, Masaharu.

In: Endocrinology, Vol. 137, No. 9, 1996, p. 3729-3737.

Research output: Contribution to journalArticle

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