Sensory nerves send the growth signals that tell broken bones to heal

Bone fractures hurt, and that pain is carried by somatosensory neurons. Evidence has also suggested that these nerves are needed to start bone regeneration. Which neurons innervate bone, and what they release to support repair, has been poorly defined. This matters for aging populations, where slow or failed fracture healing drives disability and mortality.

The researchers used single-cell transcriptomics to profile dorsal root ganglion (DRG) neurons that innervate murine bone. They did this before and after fracture, which let them see how the neurons' molecular programs change during injury and repair.

CGRP+ neurons and Aβ-Field low-threshold mechanoreceptors (LTMRs) were the most represented bone-innervating classes. After fracture, the neurons' responses changed dynamically, mirroring the phasic nature of bone repair. They included expression of morphogens such as Tgfb1, Fgf9, and Shh. When innervation was lost, bone repair was poor, with defective mesenchymal cell proliferation and osteodifferentiation. From this work the authors identified fibroblast growth factor 9 (FGF9) as a major regulator of fracture repair that could be leveraged to promote healing.

The work suggests bone healing depends on active communication from sensory nerves to progenitor cells, not only on local bone and immune signaling. It also raises the possibility that FGF9-based or other neurotrophic strategies could help in fractures with impaired healing, such as those in older adults or in people with nerve damage.

Caveats: only the abstract was available, so details on experimental design, dosing, effect sizes, and sex or age of the animals are unknown. The data come from mice, and translation to human fracture care has not been shown. Whether FGF9 can be delivered safely and effectively in people remains untested.