| Project/Area Number |
20K09482
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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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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Kagoshima University |
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Principal Investigator |
Maeda Shingo 鹿児島大学, 医歯学総合研究科, 特任教授 (60353463)
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| Co-Investigator(Kenkyū-buntansha) |
谷口 昇 鹿児島大学, 医歯学域医学系, 教授 (20626866)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | enthesis / Sox9 / Scx / 腱板損傷 / Scleraxis / 腱板再生 |
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| Outline of Research at the Start |
腱板の断裂部であるenthesisの4層構造(線維性腱部;非石灰化線維軟骨部;石灰化線維軟骨部;骨性部)の再生に必須で未知の転写因子を検索し、機能解析する。本研究では、Sox9とScxが協調的に誘導する未知のenthesisマスター遺伝子の存在を想定し、これをSox9/Scxのgain/loss-of-function後のマイクロアレイ解析で検索・同定し、間葉系幹細胞(MSC)のenthesis分化とMSC-engineered tendon形成に与える影響、さらに腱板断裂修復動物モデルの治癒への効果を評価し、臨床応用への基礎データを収集したい。
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| Outline of Final Research Achievements |
The aim of this study was to identify the genes which were cooperatively induced by Sox9 and Scleraxis (Scx) transcription factors, and analyze the functions in regeneration of enthesis. We generated adenovirus vectors that express Sox9 or Scx, then infected them into primary mouse mesenchymal stem cells. The cells were subjected to mRNA purification and direct RNA sequence analysis. Total of 224 genes with Entrez gene ID, which expression was increased by twice upon combined infection of adenoviruses expressing Sox9 and Scx, were identified. The following gene ontologies were affected; opsonization, complement activation, calcium-mediated signaling, skeletal muscle contraction, steroid metabolic process, inflammatory response, regulation of bone remodeling, and sequestering of actin monomers. KEGG pathway analysis revealed that, complement and coagulation cascades, neuroactive ligand-receptor interaction, and regulation of actin cytoskeleton were affected.
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| Academic Significance and Societal Importance of the Research Achievements |
Sox9とScxが間葉系幹細胞において協調的に誘導する遺伝子群が、オプソニン化、カルシウム・シグナル、骨格筋収縮、炎症反応、骨リモデリング制御、アクチン制御などに関わる事が示唆された。これらは、補体凝固経路、神経活性化経路、アクチン骨格制御経路などの制御に関わると予想され、既存のenthesis形成の概念からは大きく乖離した部分も大きい。興味深いのは補体活性化経路であり、無菌的な環境下でSox9とScxがなぜこれを誘導するのか、補体の新たな機能を解明するきっかけにもなるかもしれない。
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