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Pathological mechanism of osteoarthritis -analysis of molecules responsing to mechanical stress-

Research Project

Project/Area Number 18591636
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionKagoshima University

Principal Investigator

IJIRI Kosei  Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor (00315417)

Co-Investigator(Kenkyū-buntansha) KOMIYA Setsuro  Kagoshima University, Graduate School of Medical and Dental Sciences, Professor (30178371)
ISHIDOU Yasuhiro  Kagoshima University, Graduate School of Medical and Dental Sciences, Research Associate Professor (10300740)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsosteoarthritis / GADD45beta / Hypertrophic chondrocyte / 軟骨細胞 / OA / GADD45b / マウス
Research Abstract

In the next step, the expression of GADD45beta was examined using immunohistochemistry of articular cartilage from human and animal samples.
GADD45beta was especially highly expressed in cluster of early OA cartilage in human reticular cartilage. The hypertrophic chondrocyte were positive in OA animal model but not in normal animal. These findings suggested GADD45beta functions to support the mechanism of dedifferentitation of chondrocyte during the process of OA.
To examine the mechanical function of GADD45beta in terms of phenotype of chondrocyte, luciferase assay and real time PCR were performed using chondrocyte cell line. Interestingly, type X collagen and MMP-13 gene expressions were increased by GADD45beta over-expression, but decreased by GADD45beta suppressing using siRNA. Additionally, type II collagen gene expression was decreased by by GADD45beta over-expression and increased by by GADD45beta suppressing. We also investigated apoptosis analysis using ATDC5 cells. GADD45beta clearly functioned anti-apoptotic way.
This protein accelerates Type X collagen and MMP-13 gene expression and suppresses Type II collagen gene expression. GAdd45beta also noble function in terms of anti-apoptosis in chondrocyte in vitro.
These results suggest the importance of GADD45beta function in OA to support the survival of chondrocytes during the process of OA, resulting in dedifferentiation from normal chondrocyte.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (7 results)

All 2008 2006

All Journal Article (7 results) (of which Peer Reviewed: 3 results)

  • [Journal Article] Differential Expression of GADD45 β in Normal and Osteoarthritic Cartilage Potential Role in Homeostasis of Articular Chondrocytes2008

    • Author(s)
      Kosei Ijiri
    • Journal Title

      Arthritis Rheumatism 58

      Pages: 2075-2087

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] ESE-1 is a potent repressor of Type II collagen gene (COL2Al)transcription in human chondrocytes2008

    • Author(s)
      Peng H
    • Journal Title

      J Cell Physiol 215

      Pages: 562-573

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Differential Expression of GADD45β in Normal and Osteoarthritic Cartilage Potential Role in Homeostasis of Articular Chondrocytes2008

    • Author(s)
      Ijiri, K., Zerbini, L., Peng, H., Out, HH., Tsuchimochi, K., Otero, M., Dragomir, C., Walsh, N., Bierbaum, BE., Mattingly, D., Flandern, G., Komiya, S., Aigner, T., Libermann, TA., Goldring, MB
    • Journal Title

      Arthritis Rheum 58

      Pages: 2075-2087

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] ESE-1 is a Potent Pepressor of Type II Collagen Gene (LOL2A1) Transcription in Human Chondrocytes2008

    • Author(s)
      Peng, H., Tan, L., Osaki, M., Zhan, Y., Ijiri, K., Tsuchimochi, K., Otero, M., Wang, H., Choy, BK., Grail, FT., Gu, X., Libermann, TA., Oettgen, P., Goldring, MB
    • Journal Title

      J Cell Physiol 215

      Pages: 562-573

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Differential expression of GADD45b in normal and osteoarthritic cartilage: Potential role in homeostasis of articular chondrocyte2008

    • Author(s)
      Ijiri K, Zerbini FL, et. al.
    • Journal Title

      Arthritis & Rheumatism (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The cnotrol of chondrogenesis.2006

    • Author(s)
      Goldring MG, Tsuchimochi K, Ijiri K.
    • Journal Title

      J Cell Biochem 97(1)

      Pages: 33-44

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Midkine and its receptor in regenerating rat skeletal muscle after bupivacaine injection.2006

    • Author(s)
      Sakakima H, Kamizono T, Matsuda F, Izumo K, Ijiri K, Yoshida Y.
    • Journal Title

      Acta Hitochem 108(5)

      Pages: 357-63

    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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