Rotator cuff tear (RCT) is a common tendon injury, but the mechanisms of tendon healing remain incompletely understood. Elucidating the molecular mechanisms of tenogenic differentiation is essential to develop novel therapeutic strategies in clinical treatment of RCT. The long noncoding RNA H19 plays a regulatory role in tenogenic differentiation and tendon healing, but its detailed mechanism of action remains unknown. To elucidate the role of H19 in tenogenic differentiation and tendon healing, tendon-derived stem cells were harvested from the Achilles tendons of Sprague Dawley rats and a rat model of cuff tear was established for the exploration of the function of H19 in promoting tenogenic differentiation. The results showed that H19 overexpression promoted, while H19 silencing suppressed, tenogenic differentiation of tendon-derived stem cells (TDSCs). Furthermore, bioinformatic analyses and a luciferase reporter gene assay showed that H19 directly targeted and inhibited miR-140-5p to promote tenogenic differentiation. Further, inhibiting miR-140-5p directly increased VEGFA expression, revealing a novel regulatory axis between H19, miR-140-5p, and VEGFA in modulating tenogenic differentiation. In rats with RTC, implantation of H19-overexpressing TDSCs at the lesion promoted tendon healing and functional recovery. In general, the data suggest that H19 promotes tenogenic differentiation and tendon-bone healing by targeting miR-140-5p and increasing VEGFA levels. Modulation of the H19/miR-140-5p/VEGFA axis in TDSCs is a new potential strategy for clinical treatment of tendon injury.

肩袖撕裂（RCT）是一种常见的肌腱损伤，但肌腱愈合的机制仍不完全清楚。阐明肌腱分化的分子机制对于开发随机对照临床治疗的新治疗策略至关重要。长链非编码RNA H19在肌腱分化和肌腱愈合中发挥调节作用，但其详细作用机制仍不清楚。为了阐明H19在肌腱分化和肌腱愈合中的作用，从Sprague Dawley大鼠的跟腱中采集肌腱干细胞，建立大鼠袖带撕裂模型，探讨H19促进肌腱分化的功能。结果表明，H19 过表达促进腱源性干细胞 (TDSC) 的肌腱分化，而 H19 沉默则抑制腱分化。此外，生物信息学分析和荧光素酶报告基因测定表明，H19 直接靶向并抑制 miR-140-5p 以促进肌腱分化。此外，抑制 miR-140-5p 直接增加 VEGFA 表达，揭示了 H19、miR-140-5p 和 VEGFA 在调节肌腱分化方面的新调控轴。在患有 RTC 的大鼠中，在病变处植入 H19 过表达的 TDSC 可促进肌腱愈合和功能恢复。总的来说，数据表明 H19 通过靶向 miR-140-5p 和增加 VEGFA 水平来促进腱分化和腱骨愈合。 TDSC 中 H19/miR-140-5p/VEGFA 轴的调节是临床治疗肌腱损伤的一种新的潜在策略。