Boosting Sensory Nerve-to-Bone Interactions Enhances Hedgehog Mediated Calvarial Bone Repair.
Overview
Abstract
Any person that has broken a bone can attest to the existence of sensory innervation of the skeleton. Beyond afferent functions, sensory neurons have been implicated in the orchestration of bone repair via the release of neuroregulatory signals. Yet, these neurosecretory effects have principally been deciphered through loss‐of‐function studies. Indeed, the potential therapeutic benefit of boosting nerve‐to‐bone interactions remains cursorily studied. Here, using a mouse calvarial bone defect model, pharmacologic activation of TrkA with a small molecule partial agonist induced bone‐associated nerve ingrowth and significantly improved calvarial bone healing. Single‐cell RNA sequencing analysis of cells from the defect site revealed shifts in cluster proportions, with enrichment of immune cell populations in TrkA agonist‐treated mice. Within the skeletal cell lineage, TrkA agonism enhanced osteoblast differentiation while suppressing fibroblastic differentiation. Pathway analysis showed increased Hedgehog signaling activity, and interactome analyses between trigeminal ganglia sensory neurons and skeletal cells implicated Hedgehog signaling. The pro‐regenerative effects of TrkA agonism were abolished in conditional knockout mice lacking Smoothened (Smo) in PDGFRα+ skeletal progenitor cells. In summary, boosting sensory nerve signaling enhances membranous bone repair after injury, at least in part via Hedgehog pathway activation in osteoprogenitor cells.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Data links
- ncbi.nlm.nih.gov/
geo — NCBI; found in “Data Availability Statement”
Data Availability Statement
The data that support the findings of this study are openly available in NCBI GEO at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 29 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 7 keywords, 10 MeSH terms, 6 funders, 55 references.
Cite
This paper
Li, Z., Xing, X., Du, B., Zhou, M., Chen, A. Z., Archer, M., Rao, C., Zhu, M., Cherief, M., & James, A. W. (2026). Boosting Sensory Nerve-to-Bone Interactions Enhances Hedgehog Mediated Calvarial Bone Repair. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(40), e75389. https://
BibTeX
@article{li2026boosting,
author = {Li, Zhao and Xing, Xin and Du, Beicheng and Zhou, Myles and Chen, Austin Z. and Archer, Mary and Rao, Chunbao and Zhu, Manyu and Cherief, Masnsen and James, Aaron W.},
title = {{Boosting Sensory Nerve-to-Bone Interactions Enhances Hedgehog Mediated Calvarial Bone Repair}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = apr,
volume = {13},
number = {40},
pages = {e75389},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/
url = {https://
pmid = {42003742},
pmcid = {PMC13335536}
}
RIS
TY - JOUR
AU - Li, Zhao
AU - Xing, Xin
AU - Du, Beicheng
AU - Zhou, Myles
AU - Chen, Austin Z.
AU - Archer, Mary
AU - Rao, Chunbao
AU - Zhu, Manyu
AU - Cherief, Masnsen
AU - James, Aaron W.
TI - Boosting Sensory Nerve-to-Bone Interactions Enhances Hedgehog Mediated Calvarial Bone Repair
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/
VL - 13
IS - 40
SP - e75389
SN - 2198-3844
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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