Zhejiang Rehabilitation Medical Center, Hangzhou, 310051, Zhejiang, China.
Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, 310014, Zhejiang, China.
J Orthop Surg Res. 2023 May 16;18(1):361. doi: 10.1186/s13018-023-03681-0.
Achilles tendinopathy is a prevalent clinical problem that plagues athletes and general populations. Achilles tendon healing is a complex process, and so far, there is no successful long-term solution to Achilles tendinopathy in the field of microsurgery due to its poor natural regeneration ability. Limitations in understanding the pathogenesis of Achilles tendon development and Achilles tendon injury hinder clinical treatment developments. There is an increasing demand for innovative conservative treatments that can improve Achilles tendon injury. In this study, a Sprague-Dawley rat model of Achilles tendinopathy was established. Lentiviral vectors that interfere with the expression of FOXD2-AS1, miR-21-3p, or PTEN were injected every 3 days. Rats were euthanized after 3 weeks, and the effect of FOXD2-AS1, miR-21-3p, or PTEN on Achilles tendon healing was analyzed by histological observation, biomechanical test, and examinations of inflammatory factors and tendon markers. As measured, downregulating FOXD2-AS1 or upregulating miR-21-3p improved histological structure, suppressed inflammation, promoted the expression of tendon markers, and optimized the biomechanical properties of Achilles tendon. Upregulating PTEN was capable of reversing the promoting effect of inhibition of FOXD2-AS1 on Achilles tendon healing. As concluded, deficiency of FOXD2-AS1 accelerates the healing of Achilles tendon injury and improves tendon degeneration by regulating the miR-21-3p/PTEN axis and promoting the activation of the PI3K/AKT signaling pathway.
跟腱病是一种常见的临床问题，困扰着运动员和普通人群。跟腱愈合是一个复杂的过程，由于其自身较差的自然再生能力，迄今为止，在显微外科领域还没有一种成功的长期治疗跟腱病的方法。对跟腱发育和跟腱损伤发病机制的认识有限，阻碍了临床治疗的发展。人们越来越需要创新的保守治疗方法来改善跟腱损伤。在本研究中，建立了跟腱病 Sprague-Dawley 大鼠模型。每隔 3 天注射干扰 FOXD2-AS1、miR-21-3p 或 PTEN 表达的慢病毒载体。3 周后处死大鼠，通过组织学观察、生物力学试验以及炎症因子和肌腱标志物检测，分析 FOXD2-AS1、miR-21-3p 或 PTEN 对跟腱愈合的影响。结果表明，下调 FOXD2-AS1 或上调 miR-21-3p 改善了组织学结构，抑制了炎症，促进了肌腱标志物的表达，并优化了跟腱的生物力学性能。上调 PTEN 能够逆转抑制 FOXD2-AS1 对跟腱愈合的促进作用。综上所述，FOXD2-AS1 的缺乏通过调节 miR-21-3p/PTEN 轴和促进 PI3K/AKT 信号通路的激活，加速跟腱损伤的愈合并改善腱变性。
