NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone

Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA)...

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Main Authors:	Ryan E. Tomlinson, Zhi Li, Qian Zhang, Brian C. Goh, Zhu Li, Daniel L.J. Thorek, Labchan Rajbhandari, Thomas M. Brushart, Liliana Minichiello, Fengquan Zhou, Arun Venkatesan, Thomas L. Clemens
Format:	Article
Language:	English
Published:	Elsevier 2016-09-01
Series:	Cell Reports
Subjects:	sensory nerves endochondral bone nerve growth factor neurotrophic tyrosine kinase receptor type 1
Online Access:	http://www.sciencedirect.com/science/article/pii/S2211124716310348

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record_format	Article
spelling	doaj-98ef489b29e74253b6a9a78c33b2027d2020-11-24T21:36:16ZengElsevierCell Reports2211-12472016-09-0116102723273510.1016/j.celrep.2016.08.002NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral BoneRyan E. Tomlinson0Zhi Li1Qian Zhang2Brian C. Goh3Zhu Li4Daniel L.J. Thorek5Labchan Rajbhandari6Thomas M. Brushart7Liliana Minichiello8Fengquan Zhou9Arun Venkatesan10Thomas L. Clemens11Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Pharmacology, Oxford University, Oxford OX1 3QT, UKDepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USADeveloping tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA) directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkAF592A mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification.http://www.sciencedirect.com/science/article/pii/S2211124716310348sensory nervesendochondral bonenerve growth factorneurotrophic tyrosine kinase receptor type 1
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Ryan E. Tomlinson Zhi Li Qian Zhang Brian C. Goh Zhu Li Daniel L.J. Thorek Labchan Rajbhandari Thomas M. Brushart Liliana Minichiello Fengquan Zhou Arun Venkatesan Thomas L. Clemens
spellingShingle	Ryan E. Tomlinson Zhi Li Qian Zhang Brian C. Goh Zhu Li Daniel L.J. Thorek Labchan Rajbhandari Thomas M. Brushart Liliana Minichiello Fengquan Zhou Arun Venkatesan Thomas L. Clemens NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone Cell Reports sensory nerves endochondral bone nerve growth factor neurotrophic tyrosine kinase receptor type 1
author_facet	Ryan E. Tomlinson Zhi Li Qian Zhang Brian C. Goh Zhu Li Daniel L.J. Thorek Labchan Rajbhandari Thomas M. Brushart Liliana Minichiello Fengquan Zhou Arun Venkatesan Thomas L. Clemens
author_sort	Ryan E. Tomlinson
title	NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone
title_short	NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone
title_full	NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone
title_fullStr	NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone
title_full_unstemmed	NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone
title_sort	ngf-trka signaling by sensory nerves coordinates the vascularization and ossification of developing endochondral bone
publisher	Elsevier
series	Cell Reports
issn	2211-1247
publishDate	2016-09-01
description	Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA) directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkAF592A mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification.
topic	sensory nerves endochondral bone nerve growth factor neurotrophic tyrosine kinase receptor type 1
url	http://www.sciencedirect.com/science/article/pii/S2211124716310348
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NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone

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