IL-1 and TLR signals play an important role in mechanical stress-induced osteoarthritis
| Project/Area Number |
15K10492
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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 | Keio University |
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Principal Investigator |
NIKI Yasuo 慶應義塾大学, 医学部(信濃町), 准教授 (10276298)
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| Co-Investigator(Kenkyū-buntansha) |
福原 悠介 慶應義塾大学, 医学部(信濃町), 助教 (60594645)
宇田川 和彦 慶應義塾大学, 医学部(信濃町), 助教 (70528364)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | メカニカルストレス / 三次元軟骨モデル / IL-1 / TRPV4 / TLR |
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| Outline of Final Research Achievements |
We made a three-dimensional cartilage construct. ATDC5 cells were cultured in alginate beads and seeded within collagen scaffold. Cyclic compressive loading was applied to the cartilage constructs using a cyclic load bioreactor. The mRNA levels of ADAMTS4 and IL-1R1 were substantially increased by the excessive compressive stress. Compressive stress plus subtle level of IL-1β upregulated ADAMTS4 and IL-1R1 expressions. TRPV4 regulated ADAMTS4 and IL-1R1 mRNA levels by cyclic compressive stress. The expression of the IL-1R1 on the surface of chondrocytes would be stimulated by compressive mechanical stress, and subsequent increment of IL-1 susceptibility would be implicated in the OA pathology. TRPV4 channel regulation is one of the most important mechanosensor that controls IL-1 susceptibility and prevents development of OA.
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Report
(4 results)
Research Products
(4 results)
