Abstract
Bone regeneration following injury is initiated by inflammatory signals and occurs in association with infiltration by sensory nerve fibers. Together, these events are believed to coordinate angiogenesis and tissue reprogramming, but the mechanism of coupling immune signals to re-innervation and osteogenesis is unknown. Here, we found that NGF is expressed following cranial bone injury and signals via p75 in resident mesenchymal osteogenic precursors to impact their migration into the damaged tissue. Mice lacking Ngf in myeloid cells demonstrated reduced migration of osteogenic precursors to the injury site with consequently delayed bone healing. These features were phenocopied by mice lacking p75 in Pdgfra+ osteoblast precursors. Single-cell transcriptomics identified mesenchymal subpopulations with potential roles in cell migration and immune response, altered in the context of p75 deletion. Together, these results identify the role of p75 signaling pathway in coordinating skeletal cell migration during early bone repair.
Competing Interest Statement
A.W.J. is a paid consultant for Novadip and Lifesprout LLC. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. The authors declare no other competing interests.
Footnotes
Section on Results updated to clarify cell apoptosis after Ngf and p75 deletion and detect the osteogenic differentiation in human calvarial osteoblasts with or without p75 siRNA at a late time point; Figure 1,2, and 6 revised; A co-author was added; Supplemental files updated.