2005 Fiscal Year Final Research Report Summary
Gene Therapy for Periodontal Diseases -Regulation of host response by local gene delivery-
| Project/Area Number |
14370710
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Periodontal dentistry
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| Research Institution | Okayama University |
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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)
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| 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)
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| Project Period (FY) |
2002 – 2005
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| Keywords | Dentistry / Periodontal Disease / Local gene therapy / Utilization of host defense / Oral microbe / Antimicrobial peptide / Regulation of inflammation |
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| 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.
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