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microRNA29a 治疗可改善早期肌腱损伤。

MicroRNA29a Treatment Improves Early Tendon Injury.

机构信息

The Comparative Orthopedics and Regenerative Medicine Laboratory, Texas A&M University, College Station, TX 77843, USA.

Institute of Infection, Immunity, and Inflammation, College of Medicine, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.

出版信息

Mol Ther. 2017 Oct 4;25(10):2415-2426. doi: 10.1016/j.ymthe.2017.07.015. Epub 2017 Jul 28.

Abstract

Tendon injuries (tendinopathies) are common in human and equine athletes and characterized by dysregulated collagen matrix, resulting in tendon damage. We have previously demonstrated a functional role for microRNA29a (miR29a) as a post-transcriptional regulator of collagen 3 expression in murine and human tendon injury. Given the translational potential, we designed a randomized, blinded trial to evaluate the potential of a miR29a replacement therapy as a therapeutic option to treat tendinopathy in an equine model that closely mimics human disease. Tendon injury was induced in the superficial digital flexor tendon (SDFT) of 17 horses. Tendon lesions were treated 1 week later with an intralesional injection of miR29a or placebo. miR29a treatment reduced collagen 3 transcript levels at week 2, with no significant changes in collagen 1. The relative lesion cross-sectional area was significantly lower in miR29a tendons compared to control tendons. Histology scores were significantly better for miR29a-treated tendons compared to control tendons. These data support the mechanism of microRNA-mediated modulation of early pathophysiologic events that facilitate tissue remodeling in the tendon after injury and provides a strong proof of principle that a locally delivered miR29a therapy improves early tendon healing.

摘要

肌腱损伤(肌腱病)在人类和马类运动员中很常见,其特征是胶原基质失调,导致肌腱损伤。我们之前已经证明了 microRNA29a(miR29a)在调节鼠类和人类肌腱损伤中胶原 3 表达方面具有功能作用。鉴于其具有转化潜力,我们设计了一项随机、双盲试验,以评估 miR29a 替代疗法作为一种治疗马类模型中肌腱病的治疗选择的潜力,该模型非常类似于人类疾病。在 17 匹马的浅层指屈肌腱(SDFT)中诱导肌腱损伤。1 周后,通过向肌腱内注射 miR29a 或安慰剂来治疗肌腱病变。miR29a 治疗可在第 2 周降低胶原 3 的转录水平,而胶原 1 没有明显变化。与对照组相比,miR29a 肌腱的相对病变横截面积显著降低。与对照组相比,miR29a 治疗的肌腱组织学评分显著更好。这些数据支持 microRNA 介导的调节早期病理生理事件的机制,该机制促进了损伤后肌腱组织的重塑,并为局部递送 miR29a 治疗可改善早期肌腱愈合提供了强有力的原理证明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358f/5628866/859f4dfea1cc/fx1.jpg

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