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Gene Therapy for Periodontal Diseases -Regulation of host response by local gene delivery-

Research Project

Project/Area Number 14370710
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Periodontal dentistry
Research InstitutionOkayama University

Principal Investigator

TAKASHIBA Shogo  Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (50226768)

Co-Investigator(Kenkyū-buntansha) KUBOKI Takuo  Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (00225195)
NISHIMURA Fusanori  Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (80208222)
KUBOTA Satoshi  Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (90221936)
MYOKAI Fumio  Okayama University, University Hospital of Medicine and Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (50263588)
Project Period (FY) 2002 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
KeywordsDentistry / Periodontal Disease / Local gene therapy / Utilization of host defense / Oral microbe / Antimicrobial peptide / Regulation of inflammation / 遺伝子治療 / ヒトβ-defensin-2 / 顎下腺 / 唾液 / 組織再生 / 局所的遺伝子療法 / ラット唾液腺 / β-ガラクトシダーゼ / 細胞障害性 / ケミカルトランスフェクション法
Research Abstract

Because understanding the target factor was important, we decided to specify the target factor from both sides of non-specific host defense and tissue regeneration. Moreover, because it was also anxiety against clinical application of gene therapy because of its toxicity, the experiments are performed for testing it.
1.Target gene
In the rat, cytochrome c oxidase gene expressed strongly at 1 week and pro-α-2 type I collagen gene expressed strongly at 2.5 weeks after alveolar bone begun regeneration. Activation of these genes seem to be needed for alveolar bone regeneration. In dental pulp would, the homolong of human 12.7K-interacting protein 2 expressed strongly. We named it rat FIP-2 gene. It is under analyzing now for physiological meaning. In addition, inflammation, promoter region required for LPS-induced transcription of LITAF was revealed, which is new transcription factor for human tumor necrosis factor(TNF)-α.
2.Introduction of β-defensin by non-viral vector
Anti-bacterium peptide β-defensin gene was transferred to human epithelial cells and rat salivary glands to test its effect for reduce bacteria around cultured cells or rat oral cavity. Furthermore, its effect for local tissue inflammation was also examined. We found that bacterial numbers are reduced and that no obvious inflammation in rat salivary gland tissue. However, when electroporation was used for gene delivery, obvious inflammation was detected. Furthermore, It was revealed that β-defensin gene transcription requires 2 regions of NF-kB binding domain on its promoter, but that NF-IL6 biding domain on it acts to reduce its transcription.

Report

(5 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (14 results)

All 2006 2005 2004 Other

All Journal Article (12 results) Publications (2 results)

  • [Journal Article] Cloning and characterization of lipopolysaccaride-induced tumor necrosis_factor_(TNF)-α_factor_promoter.2006

    • Author(s)
      Shiomi N. et al.
    • Journal Title

      FEMS Immunology and Medical Microbiology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cloning and characterization of lipopolysaccaride-induced tumor necrosis factor (TNF)-α factor promoter.2006

    • Author(s)
      Shiomi N. et al.
    • Journal Title

      FEMS Immunology and Medical Microbiology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional regulation of β-defensin-2 by lipopolysaccharide in cultured human cervical carcinoma (HeLa) cells.2005

    • Author(s)
      Mineshiba J. et al.
    • Journal Title

      FEMS Immunology and Medical Microbiology 45・1

      Pages: 37-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Isolation and expression of FIP-2 in wounded pulp of the rat.2005

    • Author(s)
      Oyama M. et al.
    • Journal Title

      Journal of Dental Research 84・9

      Pages: 842-847

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional regulation of β-defensin-2 by lipopolysaccharide in cultured human cervical carcinoma (HeLa) cells.2005

    • Author(s)
      Mineshiba J. et al.
    • Journal Title

      FEMS Immunology and Medical Microbiology 45-1

      Pages: 37-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Isolation and expression of FIP-2 in wounded pulp of the rat.2005

    • Author(s)
      Oyama M. et al.
    • Journal Title

      Journal of Dental Research 84-9

      Pages: 842-847

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional regulation of β-defensin-2 by lipopolysaccharide in cultured human cervical carcinoma (HeLa) cells.2005

    • Author(s)
      Mineshiba J. et al.
    • Journal Title

      FEMS Immunology and Medical Microbiology 45

      Pages: 37-44

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Isolation and expression of FIP-2 in wounded pulp of the rat.2005

    • Author(s)
      Oyama M. et al.
    • Journal Title

      Journal of Dental Research 84

      Pages: 842-847

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 多糖体をキャリアとした局所的遺伝子・タンパク・細胞導入法2005

    • Author(s)
      高柴正悟
    • Journal Title

      ちゅうごく先端的医療機器等 産業クラスター創出フェア(3/7・8) (未定)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of genes differentially regulated in rat alveolar bone wound healing by subtractive hybridization.2004

    • Author(s)
      Ohira T. et al.
    • Journal Title

      Journal of Dental Research 83・7

      Pages: 546-551

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of genes differentially regulated in rat alveolar bone wound healing by subtractive hybridization.2004

    • Author(s)
      Ohira T. et al.
    • Journal Title

      Journal of Dental Research 83-7

      Pages: 546-551

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of genes differentially regulated in rat alveolar bone wound healing by subtractive hybridization2004

    • Author(s)
      Ohira T., et al.
    • Journal Title

      Journal of Dental Research 83・7

      Pages: 546-551

    • Related Report
      2004 Annual Research Report
  • [Publications] 松浦香織 et al.: "Actinobacillus actinomycetemcomitansの細胞内侵入に与えるヒトβ-defensin-2の影響"日本歯周病学会会誌. 45巻春季特別号. 81 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 峯柴淳二, 塩見信行, 峯柴 史, 松浦香織, 新井英雄, 西村英紀, 村山洋二, 高柴正悟: "唾液腺細胞への外来遺伝子の導入に関する実験的研究"日本歯周病学会会誌,秋季特別号. 44. 88 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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