| Project/Area Number |
12671821
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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 | Departmeny of Pharmacology, School of Dentistry, Aichi-Gakuin University |
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Principal Investigator |
MOGI Makio Assistant Professor, School of Dentistry, Aichi-Gakuin University, 歯学部, 講師 (00174334)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Ayami Research Associate, School of Dentistry, Aichi-Gakuin University, 歯学部, 助手 (70301629)
ARAI Michitsugu Assistant Professor, School of Dentistry, Aichi-Gakuin University, 歯学部, 講師 (20097538)
TOGARI Akifumi Professor, School of Dentistry, Aichi-Gakuin University, 歯学部, 教授 (80126325)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | osteoblasts / apoptosis / cytokine / OPG / Fas / Fasリガンド / オステオプロテグリン |
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| Research Abstract |
1) 2000〜2001 : The apoptotic signaling by proinflammatory cytokines was studied in a mouse osteoblastic cell line, MC3T3-E1 in relation to mitogen-activated protein (MAP) kinase activation. Cytokines caused potent enhancement of inducible nitric oxide synthase (iNOS) mRNA and nitric oxide (NO) in the cells. A specific inhibitor of p38MAP kinase, i.e., SB203580, inhibited the induction of iNOS mRNA, its enzyme product, NO, and DNA fragmentation (as an apoptosis index) in cytokines-treated cells in a dose-dependent manner (*p<0.01), thereby suggesting a significant role for the p38MAP kinase cascade in regulating the induction of iNOS-dependent death system in osteoblastic cells. Taken together, cytokine-induced apoptotic cell death was mediated by p38MAP kinase-dependent iNOS system in mouse osteoblastic cells (in preparation).
2) 2001〜2002 : The combination of cytokine activated the Fas-Fas Ligand (FasL)-dependent death system. Cytokines caused a potent enhancement of Fas mRNA, Fas prot
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ein, and led to apoptotic cell death. Exogenous FasL caused a decrease in cell viability and a potent increase in apoptotic cell death in the cells pretreated with cytokines, indicating that the Fas-FasL system has a potential to cause apoptosis in osteoblastic cells. Taken together, cytokine-induced apoptotic cell death was mediated by the autocrine or paracrine Fas-FasL death system in mouse osteoblastic cells (Ozeki et al., Archs Oral Biol., 2002).
3) 2002〜2003 : Osteoprotegerin (OPG) is a recently identified cytokine that belongs to the tumor necrosis factor receptor superfamily and regulates bone mass by inhibiting osteoclastic bone resorption. Bone morphogenetic protein (BMP)-4 markedly increased the level of soluble OPG in the mouse bone marrow-derived stromal cell line, ST2. BMP-4 causes the activation of p38 mitogen-activated protein (MAP) kinase using in vitro immunocomplex kinase assay, Pretreatment of ST2 cells with SB203580 inhibited the BMP-4-induced OPG. These results clearly suggest that the activation of the p38MAP kinase pathway is necessary for BMP-4-induced OPG induction in bone marrow stromal cells (Tazoe et al., Archs Oral Biol., in press). Less
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