Characterization of osteoprotegerin-induced signaling in human endothelial cells
| Project/Area Number |
22592097
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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 |
Pathobiological dentistry/Dental radiology
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| Research Institution | Hokkaido University (2011-2012)
Health Sciences University of Hokkaido (2010) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ISOGAI Emiko 東北大学, (連合)農学研究科(研究院), 教授 (80113570)
CHIBA Itsuo 北海道医療大学, 歯学部, 教授 (50250460)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 免疫 / 感染 / 炎症 / オステオプロテゲリン / 炎症性サイトカイン / トロンビン / 血管内皮細胞 |
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| Research Abstract |
Background and Objectives: Thrombin is a procoagulant and proinflammatory molecule that is also a potential mediator of bone resorption . Osteoprotegerin (OPG) is a key molecule that binds to the receptor-activator of the nuclear factor-κB (NF-κB) ligand (RANKL), and inhibits osteoclast differentiation. This study aimed to evaluate the biological effects of thrombin on OPG production in human dermal microvascular endothelial cells (HMVEC). Materials and Methods: HMVEC were treated with 2.1-11.2 U/mL of thrombin for 18 h. Thrombin-induced OPG production was assessed by enzyme-linked immunosorbent assay (ELISA). Inhibitors were used to investigate the influence of thrombin on OPG production in HMVEC and the thrombin-signaling pathway. Results: Thrombin induced OPG production in HMVEC in a dose-dependent manner. The phosphatidylinositol 3-kinase (PI3K) inhibitor and Src kinase inhibitor exerted an inhibitory effect on thrombin-induced OPG expression. Thrombin-induced OPG production was also inhibited by the protease-activated receptor (PAR)-1 antagonist. Conclusion: Thrombin induces OPG expression in HMVEC, possibly through PAR-1. Thrombin-induced OPG production is regulated by the PI3K and Src pathways. These findings suggest that thrombin may play a significant role in regulating the levels of serum OPG.
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Report
(4 results)
Research Products
(18 results)
