The study mapped the neural (somatosensory) pathways that innervate bones and monitored their changes before and after fracture in mice using single-cell transcriptomics of dorsal root ganglia (DRG) neurons.[1][4] The authors found that these bone somatosensory neurons are diverse, include both pain (nociceptive) and mechanoreceptive neurons, and their gene activity changes over time after bone injury.[1][4] Analyzes have shown that after a fracture, the expression of several signaling molecules, including Tgfb1, Fgf9 and Shh, increases significantly in the reparative phase of healing.[1] When the innervation of a fractured bone is surgically or genetically interrupted, impaired healing has been demonstrated due to a disturbance in the proliferation of mesenchymal cells and their transformation into bone cells (osteodifferentiation).[1] Single-cell RNA sequencing and interactome analyzes identified neurogenic fibroblast growth factor 9 (FGF9), released by sensory neurons, as a key regulator of fracture healing.[1][4] Targeted knockdown of FGF9 in sensory nerves in vivo confirmed that FGF9–FGFR signaling between nerves and bone reparative cells is essential for optimal fracture healing.[1][4] The study thus shows that somatosensory neurons innervating bone actively promote bone regeneration after fracture through specific neurotrophic signals, especially FGF9.[1][4]