Effects of TGF-b2 on mobilization of enthesis-related progenitor and tendon-to-bone healing in a rat rotator cuff repair model

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09481
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kumamoto University
• Principal Investigator: Tokunaga Takuya 熊本大学, 病院, 特任助教 (60759520)
• 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)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腱板修復 / enthesis / Scleraxis / Sox9 / TGF-β2 / progenitor

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.

Free Research Field

整形外科

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。