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-1 beta/TNF-alpha-rich defect niche, with consequent axonal ingrowth. In calvarial osteoblasts, IL-1 beta and TNF-alpha stimulate Ngf and downstream NF-kappa B 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.
|Titolo:||A Neurotrophic Mechanism Directs Sensory Nerve Transit in Cranial Bone|
|Data di pubblicazione:||2020|
|Appare nelle tipologie:||01.01 Articolo in Rivista|