| Project/Area Number |
20K09481
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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 | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
唐杉 樹 熊本大学, 大学院生命科学研究部(医), 講師 (80706482)
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 腱板修復 / enthesis / Scleraxis / Sox9 / TGF-β2 / progenitor / rotator cuff / tendon-to-bone healing / scleraxis / sox9 / enthesis healing |
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| Outline of Research at the Start |
腱板断裂に対する腱板修復術後の修復不全や再断裂は臨床上の課題である.近年,発生過程の研究で転写因子のScleraxis(Scx)とSox9を共発現する前駆細胞(Scx+/Sox9+細胞)が腱付着部形成に寄与し,付着部形成の制御因子の一つとしてTGF-β2が報告されている.
また,マウスモデルを用いた先行研究で,腱板損傷後の修復過程に内在性のScx+/Sox9+細胞が寄与している可能性が示唆されている.本研究では,ScxGFP遺伝子改変ラットの腱板修復モデルを用いて,TGF-β2局所投与の修復過程におけるScx+/Sox9+細胞への影響とその修復促進効果を検証し,新たな修復促進治療の確立を目指す.
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| Outline of Final Research Achievements |
Specific multipotent Scleraxis (Scx)- and Sox9-positive progenitors contribute to enthesis development. We verified the effects of TGF‐β2 on the mobilization of Scx+ and Scx+/Sox9+ progenitors and repair-promotion after rotator cuff (RC) repair in mature ScxGFP transgenic rats. We found that few Scx+ and Scx+/Sox9+ cells transiently emerged at the repair site but failed to heal fibrocartilaginous enthesis within 4 weeks after surgery in both groups; many pSmad3-positive cells were also found between the tendon and bone, suggesting sufficient endogenous TGF-β signals. In this model, TGF-β2 did not enhance the recruitment of Scx+/Sox9+ cells and regeneration of the fibrocartilage layer or increase the mechanical strength at the repair site. This may be due to the lack of endogenous progenitors that respond to TGF-β signals and contribute to healing after surgery. Our findings could lead to new strategies for establishing repair-promoting treatments after RC repair in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では成熟ラットの腱板縫合後の腱骨間の修復過程において, TGF-β2の投与による修復促進効果は認められなかった。また、成熟動物の修復過程において内在性のTGF-βシグナルはある程度充足している一方で, 線維軟骨層の修復に寄与する前駆細胞が著しく不足している可能性が示唆された。これらの結果は今後の腱板修復を促進する治療法の確立のための新たな戦略につながる知見となることが期待される。
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