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Background <p>Achilles tendinopathy is a common musculoskeletal disorder, typically caused by overuse and repetitive injury, leading to micro-damage and structural alterations of collagen fibers. Traditional treatment methods have limited efficacy. The mammalian target of&#xa0;rapamycin (mTOR) pathway, a crucial regulator of tissue repair, has emerged as a potential therapeutic target for tendinopathy.</p> Objective <p>This study aimed to evaluate the impact of the mTOR pathway inhibitor, rapamycin, on tendon healing in a collagenase-induced Achilles tendinopathy model (CITM).</p> Methods <p>Tendinopathy was induced by collagenase injection into the Achilles tendon, followed by an intraperitoneal injection of rapamycin. Tendon tissues were collected at various time points for histological, immunohistochemical, Western blot, and biomechanical analyses.</p> Results <p>Histological and immunohistochemical analyses revealed that the collagenase injection induced tendon damage. At 4- and 8-week post-injection, there was a significant upregulation in the expression of the cartilage markers Col-2 and SOX-9. Rapamycin treatment resulted in a marked reduction in cellular density and significantly improved histological scores while inhibiting Col-2 and SOX-9 expression. Western blot indicated that rapamycin effectively suppressed the mTOR signaling pathway activated by collagenase, reducing the phosphorylation levels of mTOR, AKT, and p70/S6K. Finally, biomechanical testing revealed that the diameter of the Achilles tendon normalized after rapamycin treatment, but non-significant differences in maximum mechanical load, tensile stress, or elastic modulus were observed compared to the CITM group.</p> Conclusion <p>Rapamycin effectively promotes Achilles tendon healing by inhibiting the collagenase-activated mTOR signaling pathway, particularly exhibiting potential in mitigating cartilage formation and improving histological recovery. Although its impact on biomechanical strength is limited, it may serve as a promising new strategy for treating tendinopathy.</p>

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Rapamycin-mediated inhibition of the mTOR pathway promotes tendon healing in a collagenase-induced achilles tendinopathy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月29日

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  • Eryang Zhang,
  • Xin Wang,
  • Zhikang Zhou,
  • Chen Zhang

摘要

Background

Achilles tendinopathy is a common musculoskeletal disorder, typically caused by overuse and repetitive injury, leading to micro-damage and structural alterations of collagen fibers. Traditional treatment methods have limited efficacy. The mammalian target of rapamycin (mTOR) pathway, a crucial regulator of tissue repair, has emerged as a potential therapeutic target for tendinopathy.

Objective

This study aimed to evaluate the impact of the mTOR pathway inhibitor, rapamycin, on tendon healing in a collagenase-induced Achilles tendinopathy model (CITM).

Methods

Tendinopathy was induced by collagenase injection into the Achilles tendon, followed by an intraperitoneal injection of rapamycin. Tendon tissues were collected at various time points for histological, immunohistochemical, Western blot, and biomechanical analyses.

Results

Histological and immunohistochemical analyses revealed that the collagenase injection induced tendon damage. At 4- and 8-week post-injection, there was a significant upregulation in the expression of the cartilage markers Col-2 and SOX-9. Rapamycin treatment resulted in a marked reduction in cellular density and significantly improved histological scores while inhibiting Col-2 and SOX-9 expression. Western blot indicated that rapamycin effectively suppressed the mTOR signaling pathway activated by collagenase, reducing the phosphorylation levels of mTOR, AKT, and p70/S6K. Finally, biomechanical testing revealed that the diameter of the Achilles tendon normalized after rapamycin treatment, but non-significant differences in maximum mechanical load, tensile stress, or elastic modulus were observed compared to the CITM group.

Conclusion

Rapamycin effectively promotes Achilles tendon healing by inhibiting the collagenase-activated mTOR signaling pathway, particularly exhibiting potential in mitigating cartilage formation and improving histological recovery. Although its impact on biomechanical strength is limited, it may serve as a promising new strategy for treating tendinopathy.