Regulation of onset and progression of osteoarthritis via chronic inflammation and insulin resistance in synovial tissue
| Project/Area Number |
17K11011
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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 |
Orthopaedic surgery
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| Research Institution | The University of Tokushima |
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Principal Investigator |
HAMADA Daisuke 徳島大学, 大学院医歯薬学研究部(医学域), 特任准教授 (90380097)
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| Co-Investigator(Kenkyū-buntansha) |
後東 知宏 徳島大学, 病院, 特任准教授 (10420548)
高砂 智哉 徳島大学, 大学院医歯薬学研究部(医学域), 特任助教 (40624755)
和田 佳三 徳島大学, 病院, 助教 (00771289)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 変形性関節症 / 慢性炎症 / 糖尿病 / 軟骨基質分解酵素 / 滑膜 / 基質分解酵素 / 肥満 / 関節病学 |
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| Outline of Final Research Achievements |
The expression and release of cartilage degrading enzymes such as MMP1, MMP13 and ADAMTS4 was induced by inflammatory cytokine stimulation and suppressed by insulin stimulation in osteoarthritic synoviocytes. The insulin effect was dose dependent and the higher concentration of insulin showed the most suppressive effect. The Akt phosphorylation in synovial tissue from patient with poorly controlled type2 diabetes mellitus was impaired compared to that of healthy patient. This result indicated that insulin resistance exist in synovial tissue. Insulin resistance in synovial tissue seems to accelerate the expression of cartilage degrading enzyme.
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| Academic Significance and Societal Importance of the Research Achievements |
変形性関節症における軟骨破壊は荷重ストレス等の機械的刺激が主体とされていたが、本研究成果から力学的な因子だけでなく、慢性炎症、インスリン抵抗性といった全身性因子の関与が示唆された。このことから肥満に伴う慢性炎症、インスリン抵抗性を改善できれば、滑膜からの軟骨基質分解酵素の産生抑制につながり、荷重ストレスの軽減とも併せて変形性関節症の発症や進行を抑制できる可能性が示唆された。
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Report
(4 results)
Research Products
(3 results)
