Project/Area Number |
20592425
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Periodontal dentistry
|
Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
NAGASAWA Toshiyuki Tokyo Medical and Dental University, 歯学部, 准教授 (90262203)
|
Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Hiroaki 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (50396967)
TAKEUCHI Yasuo 東京医科歯科大学, 歯学部附属病院, 医員 (60396968)
|
Project Period (FY) |
2008 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | RANKL / OPG / Wnt / beta-catenin / 抗リン脂質抗体症候群 / 感染症 / 歯学 / 免疫学 / 動脈硬化 / 細胞・組織 / 循環器・高血圧 |
Research Abstract |
Receptor activator of NF kappa B Ligand (RANKL) stimulates osteoclast differentiation, and osteoprotegerin (OPG) suppress the osteoclastogenesis. The OPG deficient mice showed severe osteopetrosis and atherosclerosis. The WNT signaling regulates cell differentiation and/or proliferation, and the activation of WNT signaling stimulates OPG expression. The purpose of this study was to examine the RANKL and OPG expression in periodontitis and atherosclerosis lesions, and evaluate the roles of periodontal infection on atherosclerosis. In addition, effects of Wnt signaling on OPG expression were also examined for the possible therapeutic approach against periodontitis and atherosclerosis. Present study showed that RANKL expression was augmented in periodontitis tissue and abdominal aortic aneurisms (AAA) tissue. In AAA tissues, periodontopathic bacteria were frequently detected, but they were completely absent in the healthy tissues. LPS from periodontopathic bacteria stimulated RANKL expression and RANKL augment MMP expression in vascular smooth muscle cells in vitro. These results suggest that RANKL expression augmented not only osteoclastogenesis, but also AAA lesion. Suppression of Wnt signaling by siRNA suppressed OPG expression in various cells. Curcumin augmented OPG expression in various cell types, suggesting that they might suppress RANKL expression in periodontitis and AAA. These results suggested that regulation of Wnt signaling might suppress periodontitis and AAA.
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