Neuronal regulation of bone and tendon injury repair: a focused review.

This review focuses on the role of peripheral sensory and sympathetic nerves in regulating the repair of bone and tendon injuries. It highlights that peripheral innervation is crucial across the three phases of musculoskeletal healing—inflammation, reparative, and remodeling—by modulating immune responses, osteogenesis, angiogenesis, and tissue remodeling through neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P (SP), as well as neurotransmitters like norepinephrine (NE) and neuropeptide Y (NPY). While bone, a highly innervated tissue, typically heals with scarless regeneration influenced by dynamic nerve interactions, tendon repair involves less direct innervation and often results in scar formation, with nerves contributing to inflammation regulation, vascularization, and scar tissue development. The review underscores the complexity of nerve-musculoskeletal crosstalk and suggests that deeper understanding of neuronal regulation may inform future therapeutic strategies for enhancing tissue healing.