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

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…

• UD
  U.S. Department of Defense

  Award: USAMRAA HT9425-24-1-0051
• AC
  American Cancer Society

  Award: DBG-23-1155131-01-IBCD
• AL
  Alex's Lemonade Stand Foundation for Childhood Cancer

  Award: 22-26743
• NI
  National Institute of Arthritis and Musculoskeletal and Skin Diseases

  Awards: R21AR078919, P01AG066603, R01AR079171
• NI
  National Institute of Dental and Craniofacial Research

  Awards: R01DE031488, R01DE031028