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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...

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Autores principales: Zhang, Jie, Wang, Liang, Cao, He, Chen, Nan, Yan, Bin, Ao, Xiang, Zhao, Huiyu, Chu, Jun, Huang, Minjun, Zhang, Zhongmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
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.
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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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