Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification

Charles Hwang; Simone Marini; Amanda K. Huber; David M. Stepien; Michael Sorkin; Shawn Loder; Chase A. Pagani; John Li; Noelle D. Visser; Kaetlin Vasquez; Mohamed A. Garada; Shuli Li; Jiajia Xu; Ching Yun Hsu; Paul B. Yu; Aaron W. James; Yuji Mishina; Shailesh Agarwal; Jun Li; Benjamin Levi

doi:10.1038/s41413-019-0075-6

Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification

Charles Hwang, Simone Marini, Amanda K. Huber, David M. Stepien, Michael Sorkin, Shawn Loder, Chase A. Pagani, John Li, Noelle D. Visser, Kaetlin Vasquez, Mohamed A. Garada, Shuli Li, Jiajia Xu, Ching Yun Hsu, Paul B. Yu, Aaron W. James, Yuji Mishina, Shailesh Agarwal, Jun Li, Benjamin Levi

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

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.

Original language	English (US)
Article number	36
Journal	Bone Research
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41413-019-0075-6
State	Published - Dec 1 2019
Externally published	Yes

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Histology
Physiology

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Hwang, C., Marini, S., Huber, A. K., Stepien, D. M., Sorkin, M., Loder, S., Pagani, C. A., Li, J., Visser, N. D., Vasquez, K., Garada, M. A., Li, S., Xu, J., Hsu, C. Y., Yu, P. B., James, A. W., Mishina, Y., Agarwal, S., Li, J., & Levi, B. (2019). Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification. Bone Research, 7(1), Article 36. https://doi.org/10.1038/s41413-019-0075-6

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title = "Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification",

abstract = "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.",

author = "Charles Hwang and Simone Marini and Huber, {Amanda K.} and Stepien, {David M.} and Michael Sorkin and Shawn Loder and Pagani, {Chase A.} and John Li and Visser, {Noelle D.} and Kaetlin Vasquez and Garada, {Mohamed A.} and Shuli Li and Jiajia Xu and Hsu, {Ching Yun} and Yu, {Paul B.} and James, {Aaron W.} and Yuji Mishina and Shailesh Agarwal and Jun Li and Benjamin Levi",

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doi = "10.1038/s41413-019-0075-6",

language = "English (US)",

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AU - Hwang, Charles

AU - Marini, Simone

AU - Huber, Amanda K.

AU - Stepien, David M.

AU - Sorkin, Michael

AU - Loder, Shawn

AU - Pagani, Chase A.

AU - Li, John

AU - Visser, Noelle D.

AU - Vasquez, Kaetlin

AU - Garada, Mohamed A.

AU - Li, Shuli

AU - Xu, Jiajia

AU - Hsu, Ching Yun

AU - Yu, Paul B.

AU - James, Aaron W.

AU - Mishina, Yuji

AU - Agarwal, Shailesh

AU - Li, Jun

AU - Levi, Benjamin

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification

Abstract

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