| Project/Area Number |
25462376
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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 | Kagoshima University |
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Principal Investigator |
Kakoi Hironori 鹿児島大学, 医歯学域医学系, 助教 (50423728)
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| Co-Investigator(Kenkyū-buntansha) |
Maeda Shingo 鹿児島大学, 医歯(薬)学総合研究科, 特任准教授 (60353463)
Komiya Setsuro 鹿児島大学, 医歯学域医学系, 教授 (30178371)
Ishidou Yasuhiro 鹿児島大学, 医歯(薬)学総合研究科, 特任准教授 (10300740)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Smpd3 / BMP / 変形性関節症 / 軟骨細胞成熟 / BMPシグナル / 軟骨細胞 |
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| Outline of Final Research Achievements |
Normal chondrocytes remain in immature state, however, chondrocytes in osteoarthritis (OA) cartilage undergo this endochondral ossification-like process, which is driven by BMP signaling.Treatment of BMP induced Smpd3 expression in a Runx2-dependent manner in chondrocytes. Loss-of-funtion of Smpd3 promoted chondrocyte maturation and Akt signaling. Smpd3 gain-of-function experiments resulted in inhibition of chondrocyte differentiation and Akt-S6 pathway.Hyaluronan (HA) synthesis was inhibited by Smpd3 via Akt pathway in chondrocytes. Hence, BMP signaling promoted OA initiation of cartilage, at the same time, it activated Smpd3 pathway to suppress Akt signaling and chondrocyte maturation as well as HA synthesis, as a negative feedback mechanism. Our results suggested that promotion of Smpd3 pathway (by application of mimicking compound like ceramide) may be valuable in treatment and/or prevention of OA progression.
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