ArticleThe Journal of clinical investigation2019
Fracture repair requires TrkA signaling by skeletal sensory nerves.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers.
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The trial behind it
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Who cites it
176 citing papers in PubMed, 245 citations in OpenAlex.
- Aptamer-functionalized EGCG nanocarrier for neutrophil-targeted AKBA delivery promotes anxiety-related fracture healing.Bioactive materials · 2027Article
- The miR-212-3p/transferrin axis promotes bone regeneration by modulating iron homeostasis through Schwann cell Exosome-BMSCs communication.Bioactive materials · 2026Article
- BMP-7 mRNA delivered by Fibrin-CaP scaffolds activates osteogenic programs in vivo as evidenced by transcriptomic and proteomic analyses.Bioactive materials · 2026Article
- Sensing the skeleton: sensorineural regulation in bone.Nature reviews. Neuroscience · 2026Review
- Unraveling stress fractures: from cellular and molecular mechanisms to therapeutic approaches.Journal of orthopaedic translation · 2026Review
- Neuropilin‑1: Emerging roles in nerve‑vessel‑bone coupling during fracture repair (Review).International journal of molecular medicine · 2026Review
- Regulating Cells Fate and Function to Facilitate Bone Regeneration via Designing Programmable Bio-Interactive Materials.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Sensory nerves regulate bone homeostasis in response to mechanical unloading or reloading: evidence from a spaceflight experiment and ground-based mechanical unloading models.Bone research · 2026Article
- Dual-gene regulation of NGF overexpression and P75NTR knockdown enhances BMSC osteogenesis by suppressing pyroptosis.iScience · 2026Article
- Dorsal Root Ganglion-Targeted DNA Origami Delivery of IL1RN for Skeletal Growth and Repair.Pharmaceutics · 2026Article
- Tissue Engineering for Massive Bone Defects: The Volumetric Scaling Problem and Strategies to Solve It.Bioengineering (Basel, Switzerland) · 2026Review
- Innovative 3D-bioprinted microfibers in calcium phosphate cement platform with Nell-1 to activate nerve-bone axis for synergistic bone, vasculature, and nanofibrous nerve regeneration.Smart molecules : open access · 2026Article
- Multidimensional bibliometric analysis and global trends in the nervous system's role in bone regeneration.Regenerative therapy · 2026Article
- Dynamic modulation of immune-neural axis via controlled magnesium-releasing nanocapsules accelerates cranial bone regeneration.Journal of nanobiotechnology · 2026Article
- Effect of neurotrophin-3 on bone healing in distraction osteogenesis.Nagoya journal of medical science · 2026Article
- Deer antler polypeptides promote osteogenesis for fracture healing via activating neurosensory PGE2/EP4/p-CREB axis.Journal of orthopaedic translation · 2026Article
- Talin1 loss activates DRG neurons to accelerate bone remodeling and fracture healing in mice.Journal of orthopaedic translation · 2026Article
- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- [Bifunctional biomaterials: An innovative strategy for synergistic bone tumor therapy and bone regeneration].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Review
- Sensory Nerve-Derived CGRP Controls Osteoclastogenesis by Limiting Macrophage Bioenergetics in Bone Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
116 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Bone is richly innervated by nerve growth factor-responsive (NGF-responsive) tropomyosin receptor kinase A-expressing (TrKa-expressing) sensory nerve fibers, which are required for osteochondral progenitor expansion during mammalian skeletal development. Aside from pain sensation, little is known regarding the role of sensory innervation in bone repair. Here, we characterized the reinnervation of tissue following experimental ulnar stress fracture and assessed the impact of loss of TrkA signaling in this process. Sequential histological data obtained in reporter mice subjected to fracture demonstrated a marked upregulation of NGF expression in periosteal stromal progenitors and fracture-associated macrophages. Sprouting and arborization of CGRP+TrkA+ sensory nerve fibers within the reactive periosteum in NGF-enriched cellular domains were evident at time points preceding periosteal vascularization, ossification, and mineralization. Temporal inhibition of TrkA catalytic activity by administration of 1NMPP1 to TrkAF592A mice significantly reduced the numbers of sensory fibers, blunted revascularization, and delayed ossification of the fracture callus. We observed similar deficiencies in nerve regrowth and fracture healing in a mouse model of peripheral neuropathy induced by paclitaxel treatment. Together, our studies demonstrate an essential role of TrkA signaling for stress fracture repair and implicate skeletal sensory nerves as an important upstream mediator of this repair process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.