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Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling
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 non-coding RNA H19 pla...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PAGEPress Publications, Pavia, Italy
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447539/ https://www.ncbi.nlm.nih.gov/pubmed/34494412 http://dx.doi.org/10.4081/ejh.2021.3297 |
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author | Liu, You-Jie Wang, Hua-Jun Xue, Zhao-Wen Cheang, Lek-Hang Tam, Man-Seng Li, Ri-Wang Li, Jie-Ruo Hou, Hui-Ge Zheng, Xiao-Fei |
author_facet | Liu, You-Jie Wang, Hua-Jun Xue, Zhao-Wen Cheang, Lek-Hang Tam, Man-Seng Li, Ri-Wang Li, Jie-Ruo Hou, Hui-Ge Zheng, Xiao-Fei |
author_sort | Liu, You-Jie |
collection | PubMed |
description | 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 non-coding 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. |
format | Online Article Text |
id | pubmed-8447539 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | PAGEPress Publications, Pavia, Italy |
record_format | MEDLINE/PubMed |
spelling | pubmed-84475392021-10-13 Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling Liu, You-Jie Wang, Hua-Jun Xue, Zhao-Wen Cheang, Lek-Hang Tam, Man-Seng Li, Ri-Wang Li, Jie-Ruo Hou, Hui-Ge Zheng, Xiao-Fei Eur J Histochem Article 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 non-coding 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. PAGEPress Publications, Pavia, Italy 2021-09-07 /pmc/articles/PMC8447539/ /pubmed/34494412 http://dx.doi.org/10.4081/ejh.2021.3297 Text en ©Copyright: the Author(s) https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Liu, You-Jie Wang, Hua-Jun Xue, Zhao-Wen Cheang, Lek-Hang Tam, Man-Seng Li, Ri-Wang Li, Jie-Ruo Hou, Hui-Ge Zheng, Xiao-Fei Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling |
title | Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling |
title_full | Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling |
title_fullStr | Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling |
title_full_unstemmed | Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling |
title_short | Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling |
title_sort | long noncoding rna h19 accelerates tenogenic differentiation by modulating mir-140-5p/vegfa signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447539/ https://www.ncbi.nlm.nih.gov/pubmed/34494412 http://dx.doi.org/10.4081/ejh.2021.3297 |
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