Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling

https://doi.org/10.4081/ejh.2021.3297

Authors

  • You-Jie Liu Department of Orthopedic Surgery and Sports Medicine Center, The First Affiliated Hospital and The First Clinical College, Jinan University, Guangzhou, China.
  • Hua-Jun Wang Department of Orthopedic Surgery and Sports Medicine Center, The First Affiliated Hospital and The First Clinical College, Jinan University, Guangzhou, China.
  • Zhao-Wen Xue Department of Orthopedic Surgery and Sports Medicine Center, The First Affiliated Hospital and The First Clinical College, Jinan University, Guangzhou, China.
  • Lek-Hang Cheang IAN WO Medical Center, Macau Special Administrative Region, Macau, China.
  • Man-Seng Tam Macau Medical Science and Technology Research Association, Macau, China.
  • Ri-Wang Li Department of Orthopedic Surgery and Sports Medicine Center, The First Affiliated Hospital and The First Clinical College, Jinan University, Guangzhou, China.
  • Jie-Ruo Li Department of Orthopedic Surgery and Sports Medicine Center, The First Affiliated Hospital and The First Clinical College, Jinan University, Guangzhou, China.
  • Hui-Ge Hou Department of Orthopedic Surgery and Sports Medicine Center, The First Affiliated Hospital and The First Clinical College, Jinan University, Guangzhou, China.
  • Xiao-Fei Zheng | zhengxiaofei12@163.com Department of Orthopedic Surgery and Sports Medicine Center, The First Affiliated Hospital and The First Clinical College, Jinan University, Guangzhou, China.

Abstract

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.

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Published
2021-09-07
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Articles
Supporting Agencies
Traditional Chinese Medicine of Guangdong Province of China, Fundamental Research Funds for the Central Universities, National Natural Science Foundation of China
Keywords:
lncRNA, miRNA, tendon stem cell, rotator cuff tear repair
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How to Cite
Liu, Y.-J., Wang, H.-J., Xue, Z.-W., Cheang, L.-H. ., Tam, M.-S. ., Li, R.-W., Li, J.-R., Hou, H.-G., & Zheng, X.-F. (2021). Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling. European Journal of Histochemistry, 65(3). https://doi.org/10.4081/ejh.2021.3297