Cargando…

Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification

Heterotopic ossification (HO) is a debilitating condition characterized by the pathologic formation of ectopic bone. HO occurs commonly following orthopedic surgeries, burns, and neurologic injuries. While surgical excision may provide palliation, the procedure is often burdened with significant int...

Descripción completa

Detalles Bibliográficos
Autores principales: Hwang, Charles, Marini, Simone, Huber, Amanda K., Stepien, David M., Sorkin, Michael, Loder, Shawn, Pagani, Chase A., Li, John, Visser, Noelle D., Vasquez, Kaetlin, Garada, Mohamed A., Li, Shuli, Xu, Jiajia, Hsu, Ching-Yun, Yu, Paul B., James, Aaron W., Mishina, Yuji, Agarwal, Shailesh, Li, Jun, Levi, Benjamin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904752/
https://www.ncbi.nlm.nih.gov/pubmed/31840004
http://dx.doi.org/10.1038/s41413-019-0075-6
_version_ 1783478051012608000
author Hwang, Charles
Marini, Simone
Huber, Amanda K.
Stepien, David M.
Sorkin, Michael
Loder, Shawn
Pagani, Chase A.
Li, John
Visser, Noelle D.
Vasquez, Kaetlin
Garada, Mohamed A.
Li, Shuli
Xu, Jiajia
Hsu, Ching-Yun
Yu, Paul B.
James, Aaron W.
Mishina, Yuji
Agarwal, Shailesh
Li, Jun
Levi, Benjamin
author_facet Hwang, Charles
Marini, Simone
Huber, Amanda K.
Stepien, David M.
Sorkin, Michael
Loder, Shawn
Pagani, Chase A.
Li, John
Visser, Noelle D.
Vasquez, Kaetlin
Garada, Mohamed A.
Li, Shuli
Xu, Jiajia
Hsu, Ching-Yun
Yu, Paul B.
James, Aaron W.
Mishina, Yuji
Agarwal, Shailesh
Li, Jun
Levi, Benjamin
author_sort Hwang, Charles
collection PubMed
description Heterotopic ossification (HO) is a debilitating condition characterized by the pathologic formation of ectopic bone. HO occurs commonly following orthopedic surgeries, burns, and neurologic injuries. While surgical excision may provide palliation, the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone. Based on these clinical observations, we set out to examine the role of vascular signaling in HO. Vascular endothelial growth factor A (VEGFA) has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis. Our findings, using a validated mouse model of HO, demonstrate that HO lesions are highly vascular, and that VEGFA is critical to ectopic bone formation, despite lacking a contribution of endothelial cells within the developing anlagen.
format Online
Article
Text
id pubmed-6904752
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-69047522019-12-13 Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification Hwang, Charles Marini, Simone Huber, Amanda K. Stepien, David M. Sorkin, Michael Loder, Shawn Pagani, Chase A. Li, John Visser, Noelle D. Vasquez, Kaetlin Garada, Mohamed A. Li, Shuli Xu, Jiajia Hsu, Ching-Yun Yu, Paul B. James, Aaron W. Mishina, Yuji Agarwal, Shailesh Li, Jun Levi, Benjamin Bone Res Article Heterotopic ossification (HO) is a debilitating condition characterized by the pathologic formation of ectopic bone. HO occurs commonly following orthopedic surgeries, burns, and neurologic injuries. While surgical excision may provide palliation, the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone. Based on these clinical observations, we set out to examine the role of vascular signaling in HO. Vascular endothelial growth factor A (VEGFA) has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis. Our findings, using a validated mouse model of HO, demonstrate that HO lesions are highly vascular, and that VEGFA is critical to ectopic bone formation, despite lacking a contribution of endothelial cells within the developing anlagen. Nature Publishing Group UK 2019-12-10 /pmc/articles/PMC6904752/ /pubmed/31840004 http://dx.doi.org/10.1038/s41413-019-0075-6 Text en © The Author(s) 2019 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hwang, Charles
Marini, Simone
Huber, Amanda K.
Stepien, David M.
Sorkin, Michael
Loder, Shawn
Pagani, Chase A.
Li, John
Visser, Noelle D.
Vasquez, Kaetlin
Garada, Mohamed A.
Li, Shuli
Xu, Jiajia
Hsu, Ching-Yun
Yu, Paul B.
James, Aaron W.
Mishina, Yuji
Agarwal, Shailesh
Li, Jun
Levi, Benjamin
Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification
title Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification
title_full Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification
title_fullStr Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification
title_full_unstemmed Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification
title_short Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification
title_sort mesenchymal vegfa induces aberrant differentiation in heterotopic ossification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904752/
https://www.ncbi.nlm.nih.gov/pubmed/31840004
http://dx.doi.org/10.1038/s41413-019-0075-6
work_keys_str_mv AT hwangcharles mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT marinisimone mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT huberamandak mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT stepiendavidm mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT sorkinmichael mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT lodershawn mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT paganichasea mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT lijohn mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT vissernoelled mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT vasquezkaetlin mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT garadamohameda mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT lishuli mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT xujiajia mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT hsuchingyun mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT yupaulb mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT jamesaaronw mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT mishinayuji mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT agarwalshailesh mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT lijun mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification
AT levibenjamin mesenchymalvegfainducesaberrantdifferentiationinheterotopicossification