Multiple factors regulate the regeneration of craniofacial bone defects. The nervous system is recognized as one of the critical regulators of bone mass, thereby suggesting a role for neuronal pathways in bone regeneration. However, in the context of craniofacial bone regeneration, little is known about the interplay between the nervous system and craniofacial bone. Sensory and sympathetic nerves interact with the bone through their neuropeptides, neurotransmitters, proteins, peptides, and amino acid derivates. The neuron-derived factors, such as semaphorin 3A (SEMA3A), substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP), possess a remarkable role in craniofacial regeneration. This review summarizes the roles of these factors and recently published factors such as secretoneurin (SN) and spexin (SPX) in the osteoblast and osteoclast differentiation, bone metabolism, growth, remodeling and discusses the novel application of nerve-based craniofacial bone regeneration. Moreover, the review will facilitate understanding the mechanism of action and provide potential treatment direction for the craniofacial bone defect.

多种因素调节颅面骨缺损的再生。神经系统被认为是骨量的关键调节剂之一，从而表明神经元通路在骨再生中的作用。然而，在颅面骨再生的背景下，神经系统和颅面骨之间的相互作用知之甚少。感觉和交感神经通过它们的神经肽、神经递质、蛋白质、肽和氨基酸衍生物与骨骼相互作用。信号素 3A (SEMA3A)、P 物质 (SP)、降钙素基因相关肽 (CGRP)、神经肽 Y (NPY) 和血管活性肠肽 (VIP) 等神经源性因子在颅面再生中具有显着的作用. 本综述总结了这些因素和最近发表的因素，如分泌神经素 (SN) 和 spexin (SPX) 在成骨细胞和破骨细胞分化、骨代谢、生长、重塑中的作用，并讨论了基于神经的颅面骨再生的新应用。此外，该综述将有助于理解作用机制，并为颅面骨缺损提供潜在的治疗方向。