| Project/Area Number |
25861303
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | University of Yamanashi |
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Principal Investigator |
WAKO Masanori 山梨大学, 総合研究部, 助教 (30402077)
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| Research Collaborator |
HARO Hirotaka 山梨大学, 総合研究部, 教授 (10313264)
ANDO Takashi 山梨大学, 総合研究部, 助教 (10377492)
SATO Nobutaka 山梨大学, 総合研究部, 助教 (00418716)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | トロンビン / PAR-1 / MCP-1 / migration / 骨折 / 組織因子 / 椎間板 / mTOR |
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| Outline of Final Research Achievements |
We herein report various effects of thrombin on mouse osteoblastic MC3T3-E1 cells. MC3T3-E1 cells expressed PAR1, also known as the coagulation factor II receptor. They also produced MCP-1, tissue factor (TF), MCSF and IL-6 upon thrombin stimulation through PI3K-Akt and MEK-Erk1/2 but not the MKK-p38 pathway. Furthermore, MCP-1 obtained from thrombin-stimulated MC3T3-E1 cells induced migration by macrophage RAW264 cells. All these effects of thrombin on MC3T3-E1 cells were abolished by the selective non-peptide thrombin receptor inhibitor SCH79797. We also found that thrombin, PAR-1, MCP-1, TF as well as phosphorylated AKT and p42/44 were significantly expressed at the fracture site of mouse femoral bone. Collectively, thrombin/PAR-1 interaction regulated MCP-1, TF, MCSF and IL-6 production by MC3T3-E1 cells. Furthermore, MCP-1 induced RAW264 cell migration. Thrombin may thus be a novel cytokine that regulates several aspects of osteoblast function and fracture healing.
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