| Project/Area Number |
26893104
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Gifu University |
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Principal Investigator |
Ogawa Hiroyasu 岐阜大学, 医学(系)研究科(研究院), 特任助教 (70464104)
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| Project Period (FY) |
2014-08-29 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 軟骨代謝 / 変形性関節症 / メカニカルストレス / 細胞外ATP / MMP13 / P2X7 / 関節軟骨 / 軟骨細胞 / 変形性膝関節症 / 運動刺激 |
|---|
| Outline of Final Research Achievements |
The signaling pathways which promote the degradation of articular cartilage in osteoarthritis have not yet been elucidated. In this work, we demonstrate that surgically induced joint destabilization or administration of Fluid Flow Shear Stress (FFSS) induces the generation of Reactive Oxygen Species (ROS) in articular chondrocytes via signaling by the extracellular ATP receptor, P2X7. We have found that joint destabilization surgery activates P2X7 signaling in articular cartilage and consequently induces both NADPH oxidase (NOX) complex-dependent elevation of ROS, which promote the activation of both ERK and p38 MAPK. The consequent phosphorylation of Jun by these kinases activates the expression of the metalloproteinase, MMP13, which in turn promotes cartilage degradation.Our findings highlight the importance of extracellular ATP/P2X7 signaling in the induction of ROS-dependent MMP13 expression in the murine surgical model for osteoarthritis.
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