| Project/Area Number |
17K10933
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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 |
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| Co-Investigator(Kenkyū-buntansha) |
前田 真吾 鹿児島大学, 医歯学総合研究科, 特任准教授 (60353463)
河村 一郎 鹿児島大学, 医歯学域鹿児島大学病院, 助教 (90535832)
小宮 節郎 鹿児島大学, 医歯学域医学系, 教授 (30178371)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 後縦靭帯骨化症 / CDC5L / WNT / GWAS / 骨芽細胞 |
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| Outline of Final Research Achievements |
The ossification of the posterior longitudinal ligament (OPLL) of the spine is an intractable disease of unknown origin, which causes severe myelopathy. We have performed a genome-wide association study to identify cell division cycle 5-like (CDC5L) gene in one of the six disease susceptibility regions. We studied its expression profile and function of CDC5L regarding osteochondrogenic differentiation. CDC5L protein was substantially expressed not only in osteoblastic and chondrocytic cells adjacent to PLL ossification area, but also in non-ligament cells such as the stromal fibrous cells in ossified area and the blood vessel cells in the ligament. Loss of Cdc5l by siRNA greatly enhanced the osteoblastic differentiation, whereas chondrogenesis was suppressed. These results suggest Cdc5l to be a molecular switch to prefer chondrogenesis from osteochondro-progenitors. CDC5L was expressed in OPLL tissue in vivo, while it suppressed osteogenesis or promoted early chondrogenesis, in vitro.
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| Academic Significance and Societal Importance of the Research Achievements |
脊椎後縦靭帯骨化症(OPLL)患者のゲノムワイド関連解析で得られた疾患感受性領域の候補遺伝子群から、CDC5L (cell division cycle 5-like)遺伝子に着目し機能解析を行った。OPLL病理組織の免疫組織化学染色による検討のほか、マウス軟骨細胞分化系や骨芽細胞分化系、骨髄由来間葉系幹細胞を用いて骨・軟骨細胞分化への影響を評価した。CDC5Lは骨軟骨前駆細胞から軟骨細胞分化への分子スイッチとも考えられ骨化initiatorの可能性が示唆された。
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