$Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion$
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Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion

Abstract There are currently no pharmacological approaches in fracture healing designed to therapeutically stimulate endochondral ossification. In this study, we test nerve growth factor (NGF) as an understudied therapeutic for fracture repair. We first characterized endogenous expression of Ngf and...

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Autores principales:	Kevin O. Rivera, Fabrizio Russo, Ryan M. Boileau, Ryan E. Tomlinson, Theodore Miclau, Ralph S. Marcucio, Tejal A. Desai, Chelsea S. Bahney
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e82164e31f174f5cb8a8bd6e7fde898b
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spelling	oai:doaj.org-article:e82164e31f174f5cb8a8bd6e7fde898b2021-12-02T12:42:27ZLocal injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion10.1038/s41598-020-78983-y2045-2322https://doaj.org/article/e82164e31f174f5cb8a8bd6e7fde898b2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78983-yhttps://doaj.org/toc/2045-2322Abstract There are currently no pharmacological approaches in fracture healing designed to therapeutically stimulate endochondral ossification. In this study, we test nerve growth factor (NGF) as an understudied therapeutic for fracture repair. We first characterized endogenous expression of Ngf and its receptor tropomyosin receptor kinase A (TrkA) during tibial fracture repair, finding that they peak during the cartilaginous phase. We then tested two injection regimens and found that local β-NGF injections during the endochondral/cartilaginous phase promoted osteogenic marker expression. Gene expression data from β-NGF stimulated cartilage callus explants show a promotion in markers associated with endochondral ossification such as Ihh, Alpl, and Sdf-1. Gene ontology enrichment analysis revealed the promotion of genes associated with Wnt activation, PDGF- and integrin-binding. Subsequent histological analysis confirmed Wnt activation following local β-NGF injections. Finally, we demonstrate functional improvements to bone healing following local β-NGF injections which resulted in a decrease in cartilage and increase of bone volume. Moreover, the newly formed bone contained higher trabecular number, connective density, and bone mineral density. Collectively, we demonstrate β-NGF’s ability to promote endochondral repair in a murine model and uncover mechanisms that will serve to further understand the molecular switches that occur during cartilage to bone transformation.Kevin O. RiveraFabrizio RussoRyan M. BoileauRyan E. TomlinsonTheodore MiclauRalph S. MarcucioTejal A. DesaiChelsea S. BahneyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kevin O. Rivera Fabrizio Russo Ryan M. Boileau Ryan E. Tomlinson Theodore Miclau Ralph S. Marcucio Tejal A. Desai Chelsea S. Bahney Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion
description	Abstract There are currently no pharmacological approaches in fracture healing designed to therapeutically stimulate endochondral ossification. In this study, we test nerve growth factor (NGF) as an understudied therapeutic for fracture repair. We first characterized endogenous expression of Ngf and its receptor tropomyosin receptor kinase A (TrkA) during tibial fracture repair, finding that they peak during the cartilaginous phase. We then tested two injection regimens and found that local β-NGF injections during the endochondral/cartilaginous phase promoted osteogenic marker expression. Gene expression data from β-NGF stimulated cartilage callus explants show a promotion in markers associated with endochondral ossification such as Ihh, Alpl, and Sdf-1. Gene ontology enrichment analysis revealed the promotion of genes associated with Wnt activation, PDGF- and integrin-binding. Subsequent histological analysis confirmed Wnt activation following local β-NGF injections. Finally, we demonstrate functional improvements to bone healing following local β-NGF injections which resulted in a decrease in cartilage and increase of bone volume. Moreover, the newly formed bone contained higher trabecular number, connective density, and bone mineral density. Collectively, we demonstrate β-NGF’s ability to promote endochondral repair in a murine model and uncover mechanisms that will serve to further understand the molecular switches that occur during cartilage to bone transformation.
format	article
author	Kevin O. Rivera Fabrizio Russo Ryan M. Boileau Ryan E. Tomlinson Theodore Miclau Ralph S. Marcucio Tejal A. Desai Chelsea S. Bahney
author_facet	Kevin O. Rivera Fabrizio Russo Ryan M. Boileau Ryan E. Tomlinson Theodore Miclau Ralph S. Marcucio Tejal A. Desai Chelsea S. Bahney
author_sort	Kevin O. Rivera
title	Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion
title_short	Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion
title_full	Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion
title_fullStr	Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion
title_full_unstemmed	Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion
title_sort	local injections of β-ngf accelerates endochondral fracture repair by promoting cartilage to bone conversion
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e82164e31f174f5cb8a8bd6e7fde898b
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Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion

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