Mapping somatosensory afferent circuitry to bone identifies neurotrophic signals required for fracture healing.

Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE

Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-

Bone and Bones*/innervation ; Fracture Healing*/physiology ; Fracture Healing*/genetics ; Fractures, Bone*/physiopathology ; Ganglia, Spinal*/cytology ; Ganglia, Spinal*/physiology ; Ganglia, Spinal*/metabolism ; Bone Regeneration* ; Nociception*; Calcitonin Gene-Related Peptide/metabolism ; Fibroblast Growth Factor 9/genetics ; Fibroblast Growth Factor 9/metabolism ; Hedgehog Proteins/metabolism ; Hedgehog Proteins/genetics ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/physiology ; Sensory Receptor Cells/physiology ; Transforming Growth Factor beta1/genetics ; Transforming Growth Factor beta1/metabolism ; Animals ; Male ; Mice ; Cell Differentiation ; Cell Proliferation ; Mice, Inbred C57BL ; Signal Transduction ; Single-Cell Analysis

The pain associated with bone fracture is mediated by somatosensory neurons, which also appear to be required to initiate bone regeneration. To characterize neuroanatomical circuitry mediating skeletal nociception and regeneration, we profiled dorsal root ganglia (DRG) neurons innervating murine bones using single-cell transcriptomics before and after fracture. CGRP⁺ and Aβ-Field LTMR neurons were the most represented classes of bone-innervating neurons. Dynamic changes in sensory neuron response to injury reflected the phasic nature of bone repair, including expression of morphogens such as Tgfb1, Fgf9, and Shh. Innervation loss resulted in poor bone repair and was associated with defective mesenchymal cell proliferation and osteodifferentiation. Finally, we identified fibroblast growth factor 9 (FGF9) as a major regulator of fracture repair that could be leveraged to promote bone repair.

Update of: bioRxiv. 2024 Jun 07:2024.06.06.597786. doi: 10.1101/2024.06.06.597786.. (PMID: 38895367)
Comment in: Science. 2026 Jan 8;391(6781):127-128. doi: 10.1126/science.aed9273.. (PMID: 41505561)

JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
0 (Fibroblast Growth Factor 9)
0 (Hedgehog Proteins)
0 (Shh protein, mouse)
0 (Tgfb1 protein, mouse)
0 (Transforming Growth Factor beta1)

Date Created: 20260108 Date Completed: 20260108 Latest Revision: 20260113

20260130

10.1126/science.adr9608

41505527