A neurotrophic mechanism directs sensory nerve transit in cranial bone
| Autor: | Zhu Li, Ye Tian, Stefano Negri, Thomas L. Clemens, Takashi Sono, Seungyong Lee, Aaron W. James, Liliana Minichiello, Sarah Miller, Carolyn A. Meyers, Leslie Chang, Jiajia Xu, Yongxing Gao, Yiyun Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Mesenchyme calvarial bone Calvaria Bone healing Biology Tropomyosin receptor kinase A General Biochemistry Genetics and Molecular Biology Article Bone and Bones osteogenesis 03 medical and health sciences Mice 0302 clinical medicine Conditional gene knockout medicine Animals lcsh:QH301-705.5 NGF Animal TrkA Skull Cell biology Disease Models Animal 030104 developmental biology Nerve growth factor medicine.anatomical_structure nervous system lcsh:Biology (General) Disease Models biology.protein Bone Remodeling bone healing 030217 neurology & neurosurgery Neurotrophin Sensory nerve |
| Zdroj: | Cell Reports, Vol 31, Iss 8, Pp-(2020) Cell reports |
| Popis: | 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. In Brief Meyers et al. describe the role of skeletal sensory nerves in cranial bone repair. The authors demonstrate several necessary aspects of membranous bone healing, including influx of nerve growth factor (NGF)-expressing macrophages after injury, followed by skeletal sensory nerve ingrowth to positively regulate bone repair. Graphical Abstract |
| Databáze: | OpenAIRE |
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