| Project/Area Number |
18592049
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
MIYAMOTO Yoichi Showa University, Department of Biochemistry, Associate Professor (20295132)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIJO Ryutaro Showa University, School of Dentistry, Department of Biochemistry, Professor (70233939)
SUZAWA Ibtsuo Showa University, School of Dentistry, Department of Biochemistry, Associate Professor (60271285)
TAKAMI Masamichi Showa University, School of Dentistry, Department of Biochemistry, Associate Professor (80307058)
YAMADA Atsushi Showa University, School of Dentistry, Department of Biochemistry, Associate Professor (50407558)
AKAIKE Takaaki Kumamoto University, Graduate School of Medical Sciences, Department of Microbiology, Professor (20231798)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | chondrocyte / odontoblast / osteoclast / nitric oxide / reactive oxygen / NADPH-oxidase / pH / differentiation / -酸化窒素 / 細胞外マトリクス / 細胞・組織 / シグナル伝達 / ストレス / 生体分子 / 生理活性 / 翻訳後修飾 / 硬組織 |
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| Research Abstract |
Nitric oxide (NO) acts as an infra- and intercellular signaling molecule. In addition to the cGMP-dependent signaling, it has been suggested that signals are transmitted by chemical modifications of biological molecules by NO and NO metabolites. In this study, we investigated the roles of NO and its metabolites in the differentiation and function of the cells which constitute hard tissues. First, we established their cell culture models. Namely, odontoblast differentiation, inflammation-induced osteoclast differentiation, and chondrocyte culture as a model of inflammatory joint diseases. We obtained the following findings using these models Expression of inducible type of NO synthase (iNOS) was induced in the pulp after abrasion of teeth without exposure of pulp. Then we studied the effects of NO on the pulp cell growth and differentiation. NO suppressed the proliferation of pulp cells and promoted the odontoblastic differentiation and mineralization, suggesting NO is involved in the f
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ormation of reparative dentin after tooth abrasion. TNF-α-induced bone resorption in ex-vivo was strongly suppressed in the iNOS-knockout calvaria In addition, osteoclast differentiation in the presence of TNF-α was retarded in the iNOS-knockout cultures NO-dependent formation of nitrated nucleotides was observed in the course of osteockast differentiation in the wild type cells. Finally, we studied the metabolism of extracellular matrix of chondmcytes after IL-1 exposure and found that IL-1 induced and activated the phagocyte-type NADPH-oxidase in the chondrocytes through the activation of TRAF-6 and NF-κB. We had already reported that IL-1 induced the expression of iNOS and formation of peroxynitrite, a reaction product of NO and superoxide in chondrocytes. The present results indicate that one of the sources of superoxide is the phagocyte type NADPH-oxidase. Interestingly, extra- and intracellular pH was decreased in the NADPH-oxidase-dependent manner, which in turn activated hyaluronidase and accelerated the loss of extracellular matrix. Less
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