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Neurotrophin‐3 acts on the endothelial‐mesenchymal transition of heterotopic ossification in rats
Despite the fact that extensive studies have focused on heterotopic ossification (HO), its molecular mechanism remains unclear. The endothelial‐mesenchymal transition (EndMT), which may be partially modulated by neuroendocrine cytokines is thought to play a major role in HO. Neurotrophin‐3 (NT‐3), w...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433730/ https://www.ncbi.nlm.nih.gov/pubmed/30672120 http://dx.doi.org/10.1111/jcmm.14150 |
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author | Zhang, Jie Wang, Liang Cao, He Chen, Nan Yan, Bin Ao, Xiang Zhao, Huiyu Chu, Jun Huang, Minjun Zhang, Zhongmin |
author_facet | Zhang, Jie Wang, Liang Cao, He Chen, Nan Yan, Bin Ao, Xiang Zhao, Huiyu Chu, Jun Huang, Minjun Zhang, Zhongmin |
author_sort | Zhang, Jie |
collection | PubMed |
description | Despite the fact that extensive studies have focused on heterotopic ossification (HO), its molecular mechanism remains unclear. The endothelial‐mesenchymal transition (EndMT), which may be partially modulated by neuroendocrine cytokines is thought to play a major role in HO. Neurotrophin‐3 (NT‐3), which has neuroendocrine characteristics is believed to promote skeletal remodeling. Herein, we suggest that that NT‐3 may promote HO formation through regulation of EndMT. Here, we used an in vivo model of HO and an in vitro model of EndMT induction to elucidate the effect and underlying mechanism of NT‐3 on EndMT in HO. Our results showed that heterotopic bone and cartilage arose from EndMT and NT‐3 promoted HO formation in vivo. Our in vitro results showed that NT‐3 up‐regulated mesenchymal markers (FSP‐1, α‐SMA and N‐cadherin) and mesenchymal stem cell (MSC) markers (STRO‐1, CD44 and CD90) and down‐regulated endothelial markers (Tie‐1, VE‐cadherin and CD31). Moreover, NT‐3 enhanced a chondrogenesis marker (Sox9) and osteogenesis markers (OCN and Runx2) via activation of EndMT. However, both EndMT specific inhibitor and tropomyosin‐related kinase C (TrkC) specific inhibitor rescued NT‐3‐induced HO formation and EndMT induction in vivo and in vitro. In conclusion, our findings demonstrate that NT‐3 promotes HO formation via modulation of EndMT both in vivo and in vitro, which offers a new potential target for the prevention and therapy of HO. |
format | Online Article Text |
id | pubmed-6433730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64337302019-04-08 Neurotrophin‐3 acts on the endothelial‐mesenchymal transition of heterotopic ossification in rats Zhang, Jie Wang, Liang Cao, He Chen, Nan Yan, Bin Ao, Xiang Zhao, Huiyu Chu, Jun Huang, Minjun Zhang, Zhongmin J Cell Mol Med Original Articles Despite the fact that extensive studies have focused on heterotopic ossification (HO), its molecular mechanism remains unclear. The endothelial‐mesenchymal transition (EndMT), which may be partially modulated by neuroendocrine cytokines is thought to play a major role in HO. Neurotrophin‐3 (NT‐3), which has neuroendocrine characteristics is believed to promote skeletal remodeling. Herein, we suggest that that NT‐3 may promote HO formation through regulation of EndMT. Here, we used an in vivo model of HO and an in vitro model of EndMT induction to elucidate the effect and underlying mechanism of NT‐3 on EndMT in HO. Our results showed that heterotopic bone and cartilage arose from EndMT and NT‐3 promoted HO formation in vivo. Our in vitro results showed that NT‐3 up‐regulated mesenchymal markers (FSP‐1, α‐SMA and N‐cadherin) and mesenchymal stem cell (MSC) markers (STRO‐1, CD44 and CD90) and down‐regulated endothelial markers (Tie‐1, VE‐cadherin and CD31). Moreover, NT‐3 enhanced a chondrogenesis marker (Sox9) and osteogenesis markers (OCN and Runx2) via activation of EndMT. However, both EndMT specific inhibitor and tropomyosin‐related kinase C (TrkC) specific inhibitor rescued NT‐3‐induced HO formation and EndMT induction in vivo and in vitro. In conclusion, our findings demonstrate that NT‐3 promotes HO formation via modulation of EndMT both in vivo and in vitro, which offers a new potential target for the prevention and therapy of HO. John Wiley and Sons Inc. 2019-01-22 2019-04 /pmc/articles/PMC6433730/ /pubmed/30672120 http://dx.doi.org/10.1111/jcmm.14150 Text en © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Zhang, Jie Wang, Liang Cao, He Chen, Nan Yan, Bin Ao, Xiang Zhao, Huiyu Chu, Jun Huang, Minjun Zhang, Zhongmin Neurotrophin‐3 acts on the endothelial‐mesenchymal transition of heterotopic ossification in rats |
title | Neurotrophin‐3 acts on the endothelial‐mesenchymal transition of heterotopic ossification in rats |
title_full | Neurotrophin‐3 acts on the endothelial‐mesenchymal transition of heterotopic ossification in rats |
title_fullStr | Neurotrophin‐3 acts on the endothelial‐mesenchymal transition of heterotopic ossification in rats |
title_full_unstemmed | Neurotrophin‐3 acts on the endothelial‐mesenchymal transition of heterotopic ossification in rats |
title_short | Neurotrophin‐3 acts on the endothelial‐mesenchymal transition of heterotopic ossification in rats |
title_sort | neurotrophin‐3 acts on the endothelial‐mesenchymal transition of heterotopic ossification in rats |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433730/ https://www.ncbi.nlm.nih.gov/pubmed/30672120 http://dx.doi.org/10.1111/jcmm.14150 |
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