A Neurotrophic Mechanism Directs Sensory Nerve Transit in Cranial Bone

Carolyn A. Meyers; Seungyong Lee; Takashi Sono; Jiajia Xu; Stefano Negri; Ye Tian; Yiyun Wang; Zhu Li; Sarah Miller; Leslie Chang; Yongxing Gao; Liliana Minichiello; Thomas L. Clemens; Aaron W. James

Cell Reports (May 2020)

A Neurotrophic Mechanism Directs Sensory Nerve Transit in Cranial Bone

Carolyn A. Meyers,
Seungyong Lee,
Takashi Sono,
Jiajia Xu,
Stefano Negri,
Ye Tian,
Yiyun Wang,
Zhu Li,
Sarah Miller,
Leslie Chang,
Yongxing Gao,
Liliana Minichiello,
Thomas L. Clemens,
Aaron W. James

Affiliations

Carolyn A. Meyers: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
Seungyong Lee: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
Takashi Sono: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
Jiajia Xu: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
Stefano Negri: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Orthopaedics and Traumatology, University of Verona, 37129 Verona, Italy
Ye Tian: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
Yiyun Wang: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
Zhu Li: Department of Orthopaedics, Johns Hopkins University, Baltimore, MD 21205, USA; Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA
Sarah Miller: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
Leslie Chang: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
Yongxing Gao: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
Liliana Minichiello: Department of Pharmacology, Oxford University, Oxford OX1 3QT, UK
Thomas L. Clemens: Department of Orthopaedics, Johns Hopkins University, Baltimore, MD 21205, USA; Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA; Corresponding author and
Aaron W. James: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA; Corresponding author

Journal volume & issue: Vol. 31, no. 8

Abstract

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Summary: The flat bones of the skull are densely innervated during development, but little is known regarding their role during repair. We describe a neurotrophic mechanism that directs sensory nerve transit in the mouse calvaria. Patent cranial suture mesenchyme represents an NGF (nerve growth factor)-rich domain, in which sensory nerves transit. Experimental calvarial injury upregulates Ngf in an IL-1β/TNF-α-rich defect niche, with consequent axonal ingrowth. In calvarial osteoblasts, IL-1β and TNF-α stimulate Ngf and downstream NF-κB signaling. Locoregional deletion of Ngf delays defect site re-innervation and blunted repair. Genetic disruption of Ngf among LysM-expressing macrophages phenocopies these observations, whereas conditional knockout of Ngf among Pdgfra-expressing cells does not. Finally, inhibition of TrkA catalytic activity similarly delays re-innervation and repair. These results demonstrate an essential role of NGF-TrkA signaling in bone healing and implicate macrophage-derived NGF-induced ingrowth of skeletal sensory nerves as an important mediator of this repair.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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