Tissue repair relies on the coordination of mesenchymal precursor cells (MPCs) which migrate into the injury site, along with the invasion of blood vessels and sensory nerves. Our prior observations found that the neurotrophin Nerve growth factor (NGF) regulates sensory nerve ingrowth to skeletal repair sites via its high-affinity receptor. A body of work in cancer biology suggest that neurotrophins also engage their low-affinity receptor p75 to mediate cellular migration. Here, we observed conditional deletion of p75 in MPCs or osteoblasts to disrupt bone repair independent of neurovascular ingrowth. Single cell sequencing identified defects in migration and wound healing among MPC populations. Deletion of Ngf among myeloid cells phenocopied p75 conditional deletion animals. In vitro studies confirmed a myeloid-to-mesenchymal NGF-p75 axis which operates to induce cellular migration. Together, our data suggest a direct effect of myeloid-derived NGF on progenitor cells, in parallel to sensory nerve recruitment, required for injury repair.
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