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Gene therapy for temporomandibular joint osteoarthritis

Research Project

Project/Area Number 12557169
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 補綴理工系歯学
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

KUBOKI Takuo  Okayama University Graduate School of Medicine and Dentistry Associate Professor, 大学院・医歯学総合研究科, 助教授 (00225195)

Co-Investigator(Kenkyū-buntansha) NAKANISHI Tohru  Okayama University Graduate School of Medicine and Dentistry Associate Professor, 大学院・医歯学総合研究科, 助教授 (30243463)
TAKIGAWA Masaharu  Okayama University Graduate School of Medicine and Dentistry Professor, 大学院・医歯学総合研究科, 教授 (20112063)
FUJISAWA Takuo  Okayama University Graduate School of Medicine and Dentistry Research Associate, 大学院・医歯学総合研究科, 助手 (20325096)
KASAI Teruo  Okayama University Dental Hospital Research Associate, 大学院・医歯学総合研究科, 助教授 (00335613)
YATANI Hirofumi  Okayama University Graduate School of Medicine and Dentistry Professor, 大学院・医歯学総合研究科, 教授 (80174530)
完山 学  岡山大学, 歯学部・附属病院, 講師 (90294420)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2002: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2000: ¥4,200,000 (Direct Cost: ¥4,200,000)
KeywordsOsteoarthritis / Mechanical stress / Articular cartilage / Gene therapy / Adenovirus / Chondrocyte / 軟骨破壊 / アポトーシス / 一酸化窒素 / マトリックスメタロプロテアーゼ / 動物モデル / 組織変化 / 遺伝子導入 / アデノウイルスベクター / CTGF / 培養軟骨細胞 / 細胞分化 / 細胞増殖 / 遺伝子発現
Research Abstract

The purposes of this research are to clarify the mechanism of cartilage degradation in osteoarthritis (OA) and to investigate the possibility of gene therapy for articular cartlige restoration using connective tissue growth fector (CTGF).
First, we establish a genuine mechanical-stress-induced OA model of the rabbit TMJ. In the experimental rabbits, repetitive forced jaw opening (RFJO) 3 hours/day for 5 days was applied. By histological assessment of the TMJ articular tissues, partial eburnation of the articular cartilage, reactive marginal proliferation of the articular cartilage chondrocytes and nested proliferation of chondrocytes in the subchondral bone area were observed at 7 days after the RFJO period. These results suggest the RFJO protocol without any surgical intervention can induce evident OA-like lesions in the rabbit TMJ, and this OA model may greatly contribute to the elucidation of the cartilage degradation mechanism in TMJ OA.
Second, we investigated the effects of CTGF/Hcs24 transduced by recombinant adenoviruses on the rabbit articular cartilage (RAC) cells in vitro. When RAC cells were infected with adenoviruses caontaining the CTGF/Hcs24 gene, RAC cells expressed CTGF/Hcs24 mRNA and produced CTGF/Hcs24 protein. RAC cells synthesized more proteoglycan than the control cells.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] T.Kuboki et al.: "CTGF/Hcs24, a hypertrophic chondrocytes specific gene product, stimulates proliferation and differentiation, but not hypertrophy of cultured articular chondrocytes"J Cellular Physiol.. 192. 55-63 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T Kuboki et al.: "Soluble tumor necrosis factor receptors are up-regulated in synovial fluids from osteoarthritic temporomandibular joints"Archs Oral Biol. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T Fujisawa et al.: "A repetitive mouth opening induced osteoarthritis-like lesion in rabbit temporomandibular joint"J Dent Res. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Nishida, S. Kubota, T. Nakanishi, T. Kuboki, G. Yoshimichi, S. Kondo, M. Takigawa: "CTGF/Hcs24, a hypertrpphic chondrocytes specific gene product, stimulates proliferation and differentiation, but not hypertrophy of cultured articular chondrocytes"J Cellular Physiol.. 192(1). 55-63 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] J. Uehara, T. Kuboki, T. Fujisawa, S. Kojima, K. Maekawa, H. Yatani: "Soluble tumor necrosis factor receptors are up-regulated in synovial fluids from osteoarthritic temporomandibular joints, preliminarily accepted"Archs Oral Biol.. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Fujisawa, T. Kuboki, T. Kasai, W. Sonoyama, S. Kojima, J. Uehara, C. Komori, H. Yatani, T. Hattori, M. Takigawa: "A repetitive mouth opening induced osteoarthritis-like lesion in rabbit temporomandibular joint, preliminarily accepted"J Dent Res.. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Fujisawa et al.: "NO Production in Mechanical-Stress-Induced OA Cartilage of the Rabbit TMJ"Journal of Dental Research. 81. 379 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 窪木拓男 他: "骨軟骨組織修復における結合組織成長因子CTGF/Ecogeninの役割"第4回生体組織工学シンポジウム-Biological Tissue Engineering-資料集. 107-121 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujisawa T et al.: "Chondrocyte apoptosis in mechanical-stress-induced OA cartilage of the rabbit TMJ"Journal of Dental Research (AADR abstract). 80. 88 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanyama M et al.: "Adenovirus-mediated CTGF gene delivery to cultured osteoblast in vitro"Journal of Dental Research (AADR abstract). 80. 266 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kuboki T et al.: "Effect of CTGF/Hcs24 on proliferation/differentiation of articular chondrocytes in culture"Journal of Dental Research (IADR abstract). 80. 634 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 藤沢拓生: "軟骨由来軟骨成長因子(CTGF/Hcs24)を用いた関節軟骨再生療法の検討"第14回日本顎関節学会総会・学術大会プログラム・抄録集. 76 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 藤沢拓生: "ウサギ変形性顎関節症モデルにおける軟骨細胞のアポトーシスの関与"第14回日本顎関節学会総会・学術大会プログラム・抄録集. 114 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 窪木拓男: "関節軟骨細胞の増殖・基質合成・石灰化の対する結合組織成長因子の影響"日本補綴歯科学会雑誌. 45. 181 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakanishi et al.: "Effects of CTGF/Hcs24, a product of a hypertrophic chondrocyte-specific gene, on the proliferation and differentiation of chondrocytes in culture"Endocrinology. 141(1). 264-273 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 完山学 ほか: "アデノウイルスベクターによる培養骨芽細胞と骨組織への結合組織成長因子の遺伝子導入"日本補綴歯科学会雑誌. 44(104). 196 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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