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2005 Fiscal Year Final Research Report Summary

On the regulation of survival and death of synoviocytes and chondrocytes by nitric oxide

Research Project

Project/Area Number 16591865
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionShowa University

Principal Investigator

MIYAMOTO Yoichi  Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (20295132)

Co-Investigator(Kenkyū-buntansha) KATAGIRI Takenobu  Saitama Medical School, Research Center for Genomic Medicine, Associate Professor, ゲノム医学研究センター, 助教授 (80245802)
MASAMICHI Takami  Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (80307058)
SHINKI Toshimasa  Nihon Pharmaceutical University, Department of Biochemistry, Professor, 薬学部, 教授 (90138420)
MORIMURA Naoko  Riken, Brain Science Institute, Researcher, 脳科学総合研究センター, 研究員 (00349044)
KAMIJO Ryutaro  Showa University, School of dentistry, Professor, 歯学部, 教授 (70233939)
Project Period (FY) 2004 – 2005
Keywordsnitric oxide / chondrocytes / synoviocytes / cell death / rheumatoid arthritis / osteoarthritis / NADPH-oxidase / radicals
Research Abstract

It is known that nitric oxide production is up-regulated both in synovial tissues and articular cartilages in the joints of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. NO is regarded as one of the important molecules to regulate cell death and survival, whereas the regulatory mechanism has not been fully elucidated. On the other hand, interleukin-1 (IL-1) acts as a key mediator of the degeneration of articular cartilage in RA and OA, where chondrocyte death is observed. In this study, the viability of mouse chondrocyte-like ATDC5 cells was reduced by the treatment with IL-1β for 48 h or longer. IL-1β augmented the expression of the catalytic subunit of NADPH-oxidase gp91^<phox> as well as inducible NO synthase in ATDC5 cells. Generation of nitrated guanosine and tyrosine suggested the formation of reactive nitrogen species including peroxynitrite (ONOO^-), a reaction product of NO and superoxide in ATDC5 cells and rat primary chondrocytes treated with IL-1β. Death of AT … More DC5 cells after IL-1β treatment was prevented by an NADPH-oxidase inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride (AEBSF), a NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME), and a ONOO^- scavenger uric acid. The viability of ATDC5 cells was reduced by a ONOO^- generator 3-(4-morpholinyl)sydnonimine hydrochloride but not by either a NO donor 1-hydroxy-2-oxo-3-(N-methyl-2-aminopropyl)-3-methyl-1-triazene or S-nitrosoglutathione. Disruption of mitochondrial membrane potential and ATP deprivation were observed in IL-1β-treated ATDC5 cells, both of which were restored by L-NAME, AEBSF, or uric acid. On the other hand, any morphological or biochemical sign indicating apoptosis was not observed in these cells. These results suggest that the death of chondrocyte-like ATDC5 cells was mediated at least in part by mitochondrial dysfunction and energy depletion through ONOO^- formation after IL-1β treatment. We have also succeeded in the establishment of a fibroblastic cell line from the synoviocytes obtained from an RA patient. Less

  • Research Products

    (4 results)

All 2005

All Journal Article (4 results)

  • [Journal Article] IL-1誘導性の軟骨細胞死における一酸化窒素の役割2005

    • Author(s)
      安原理佳
    • Journal Title

      口腔組織培養学会誌 14・1

      Pages: 55-56

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Interleukin-1β induces death in chondrocyte-like ATDC5 cells through mitochondrial dysfunction and energy depletion in a reactive nitrogen and oxygen species-dependent manner.2005

    • Author(s)
      Yasuhara. R
    • Journal Title

      Biochem. J. 389・2

      Pages: 315-323

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Role of nitric oxide in the IL-1-induced chondrocyte death.2005

    • Author(s)
      Yasuhara, R., et al.
    • Journal Title

      Jpn.J.tissue Cult.Dent.Res. 14

      Pages: 55-56

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Interleukin-1β induces death of chondrocyte-like ATDC5 cells through mitochondrial dysfunction and energy depletion in a reactive nitrogen and oxygen species-dependent manner.2005

    • Author(s)
      Yasuhara, R., et al.
    • Journal Title

      Biochem.J. 389

      Pages: 315-323

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2007-12-13  

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