Crosstalk between skeletal and neural tissues is critical for skeletal health

Emerging evidence in the literature describes a physical and functional association between the neural and skeletal systems that forms a neuro-osteogenic network. This communication between bone cells and neural tissues within the skeleton is important in facilitating bone skeletal growth, homeostasis and repair. The growth and repair of the skeleton is dependent on correct neural innervation for correct skeletal developmental growth and fracture repair, while pathological conditions such as osteoporosis are accelerated by disruptions to sympathetic innervation. To date, different molecular mechanisms have been reported to mediate communication between bone and neural populations. This review highlights the important role of various cell surface receptors, cytokines and associated ligands as potential regulators of skeletal development, homeostasis, and repair, by mediating interactions between the skeletal and nervous systems. Specifically, this review describes how Bone Morphogenetic Proteins (BMPs), Eph/ephrin, Chemokine CXCL12, Calcitonin Gene-related Peptide (CGRP), Netrins, Neurotrophins (NTs), Slit/Robo and the Semaphorins (Semas) contribute to the cross talk between bone cells and peripheral nerves, and the importance of these interactions in maintaining skeletal health.