Fig. 4
From: Hallmarks of peripheral nerve function in bone regeneration
Illustration showing how PNS nerve fibers regulate bone regenerative processes following injury. The basic regeneration processes are represented by blue arrows. Neuropeptides or neurotransmitters positively or negatively regulate osteoblastic differentiation in MSCs, osteoclastogenesis in monocytes, tube formation by endothelial cells, type switching in macrophages and the recruitment of immune cells during the inflammatory phase of bone regeneration. Dedifferentiated SCs and endoneurium mesenchymal precursor cells contribute to new bone formation via direct osteoblastic differentiation or indirect secretion to stimulate the differentiation of MSCs. Red arrowheads represent a stimulatory effect, while green flatheads represent an inhibitory effect. Green boxes contain stimulative neuropeptides or neurotransmitters for the corresponding process, and blue boxes contain suppressive neuropeptides or neurotransmitters. “?” indicates that more reliable evidence is needed. CGRP calcitonin gene‐related peptide, SP substance P, NE norepinephrine, NPY neuropeptide Y, VIP vasoactive intestinal peptide, NGF nerve growth factor, BDNF brain-derived neurotrophic factor, NT-3 neurotrophin-3, Sema3A Semaphorin 3A, Sema3E Semaphorin3E, Sema4D Semaphorin4D
