Elucidation of the molecular mechanisms that the axis of the HIF-1 in the joint contracture: the development of new molecular therapeutic formulation
| Project/Area Number |
24590906
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General internal medicine (including Psychosomatic medicine)
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| Research Institution | Morinomiya University of Medical Sciences |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Motokuni 森ノ宮医療大学, 保健医療学部, 教授 (00346214)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 関節拘縮 / 滑膜 / 線維化 / HIF-1 / デコイ核酸医薬 / HIF1-α / CTGF / VEGF / HIF / ＣＴＧＦ / HIF1α |
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| Outline of Final Research Achievements |
Although limited range of motion (ROM) by joint contracture occurred in joint immobilized treatment, its molecular mechanism is not fully clarified. In this study we investigated its histological and molecular mechanism. In a animal model ROM of an immobilized knee was decreased with time followed by capsule fibrosis. In addition, hypoxia inducible factor-1 (HIF-1) was activeted and CTGF and VEGF was up-regulated in both mRNA and protein levels after immobilization.
Of importance, intra-articular transfection of ribbon-type decoy oligonucleotides (ODN) for HIF-1 in the animal model resulted in attenuation of increased expressions of CTGF and VEGF followed by synovial thickening and restricted ROM. This study suggested the important role of HIF-1 in the pathogenesis of immobilization-induced joint contracture, and provides the possibility of the molecular treatment for joint contracture using practical methodology before the intervention of physical therapy.
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Report
(4 results)
Research Products
(5 results)
