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

J Bone Miner Res. 2024 Aug 21;39(8):1045-1060. doi: 10.1093/jbmr/zjae087.

Abstract

Beyond the sensation of pain, peripheral nerves have been shown to play crucial roles in tissue regeneration and repair. As a highly innervated organ, bone can recover from injury without scar formation, making it an interesting model in which to study the role of nerves in tissue regeneration. As a comparison, tendon is a musculoskeletal tissue that is hypo-innervated, with repair often resulting in scar formation. Here, we reviewed the significance of innervation in 3 stages of injury repair (inflammatory, reparative, and remodeling) in 2 commonly injured musculoskeletal tissues: bone and tendon. Based on this focused review, we conclude that peripheral innervation is essential for phases of proper bone and tendon repair, and that nerves may dynamically regulate the repair process through interactions with the injury microenvironment via a variety of neuropeptides or neurotransmitters. A deeper understanding of neuronal regulation of musculoskeletal repair, and the crosstalk between nerves and the musculoskeletal system, will enable the development of future therapies for tissue healing.

Keywords: bone injury; peripheral nervous system; tendon injury; tissue repair and regeneration.

Plain language summary

Accumulating evidence has shown that, across organs systems, peripheral nerves regulate the process of tissue repair and regeneration. This is particularly relevant in the context of musculoskeletal injuries such as those affecting the bone and tendon. The question then arises: what is the function of peripheral innervation in the repair of bone and tendon injuries? This review offers an in-depth look at the ways in which nerves regulate the healing of bone and tendon injuries at various stages of recovery. A deeper comprehension of the influence of nerves on the repair of these tissues could pave the way for the development of future therapeutic strategies for tissue healing.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone and Bones* / pathology
  • Humans
  • Neurons / metabolism
  • Neurons / pathology
  • Tendon Injuries* / pathology
  • Tendon Injuries* / physiopathology
  • Tendons / pathology
  • Tendons / physiopathology
  • Wound Healing*