[PDF][PDF] A neurotrophic mechanism directs sensory nerve transit in cranial bone

CA Meyers, S Lee, T Sono, J Xu, S Negri, Y Tian… - Cell reports, 2020 - cell.com
CA Meyers, S Lee, T Sono, J Xu, S Negri, Y Tian, Y Wang, Z Li, S Miller, L Chang, Y Gao
Cell reports, 2020cell.com
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 …
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.
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