2006 Fiscal Year Final Research Report Summary
Establishment of periodontitis treatment method by inhibition of RANK-Toll like receptor signal
| Project/Area Number |
17390497
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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 |
Functional basic dentistry
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| Research Institution | Matsumoto Dental University |
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Principal Investigator |
UDAGAWA Nobuyuki Matsumoto Dental University, Department of dentistry, Professor, 歯学部, 教授 (70245801)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Hiroaki Matsumoto Dental University, Department of dentistry, Professor, 歯学部, 教授 (50227930)
YAMASHITA Teruhito Matsumoto Dental University, Institute of Oral Science, Lecturer, 総合歯科医学研究所, 講師 (90302893)
NAKAMURA Midori Matsumoto Dental University, Department of dentistry, Lecturer, 歯学部, 講師 (90278177)
NAKAMICHI Yuko Matsumoto Dental University, Institute of Oral Science, Assistant, 総合歯科医学研究所, 助手 (20350829)
MIZOGUCHI Toshihide Matsumoto Dental University, Institute of Oral Science, Lecturer, 総合歯科医学研究所, 講師 (90329475)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Osteoclast / LPS / RANKL / M-CSF / CD14 / MyD88 / PKC / TRIF |
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| Research Abstract |
MDP, the minimal essential structural unit responsible for the immunoadjuvant activity of peptidoglycans, is distributed ubiquitously in cell walls of both Gram-negative and-positive bacteria. MDP has been shown to exert diverse biological effects on immunocompetent cells. We have shown that injection of MDP into mice resulted in endotoxin hypersensitivity : enhanced production of TNF-α and lethal shock upon challenge injection of LPS. We also showed that MDP synergistically enhanced LPS-induced proinflammatory cytokine production in human monocytic cells. Recently, it was proposed that nucleotide-binding oligomerization domain (Nod) 2, a member of the Apaf1/Nod protein family, is an intracellular sensor of MDP. Nod2 consists of an N-terminal caspase-recruitment domain, a centrally located nucleotide-binding domain and C-terminal leucine-rich repeats, and acts as a signal-transducing adaptor. Nod2 expression is enhanced by proinflammatory cytokines and LPS. 1 α,25(OH)2D3, PGE2, LPS and
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IL-1 a stimulate osteoclast formation in mouse cocultures of osteoblasts and hemopoietic cells. MDP alone could not induce osteoclast formation in the coculture, but enhanced osteoclast formation induced by LPS, IL-1α or TNF-α but not 1 α,25(OH)2D3 or PGE2. MDP failed to enhance osteoclast formation from osteoclast progenitors induced by RANKL or TNF-α. MDP up-regulated RANKL expression in osteoblasts treated with LPS or TNF-α but not 1 α,25(OH)2D3. Osteoblasts expressed mRNA of Nod2 in response to LPS, IL-1α or TNF-α but not 1 α,25(OH)2D3. Induction of Nod2 mRNA expression by LPS but not by TNF-α in osteoblasts was dependent on TLR4 and MyD88. The depletion of intracellular Nod2 by small interfering RNA blocked MDP-induced up-regulation of RANKL mRNA in osteoblasts. LPS and RANKL stimulated the survival of osteoclasts, and this effect was not enhanced by MDP. These results suggest that MDP synergistically enhances osteoclast formation induced by LPS, IL-1α and TNF-a through RANKL expression in osteoblasts, and that Nod2-mediated signals are involved in the MDP-induced RANKL expression in osteoblasts. Less
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Research Products
(14 results)
