ArticleNature communications2021
NGF-TrkA signaling dictates neural ingrowth and aberrant osteochondral differentiation after soft tissue trauma.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 83 citations in OpenAlex.
- Sensing the skeleton: sensorineural regulation in bone.Nature reviews. Neuroscience · 2026Review
- Clec3bBone research · 2026Article
- Chronic stress drives gastric cancer lymph node metastasis via NETosis through a feedforward ACh-NGF axis-mediated PKC-γ/STAT3 pathway.Oncogene · 2026Article
- Talin1 loss activates DRG neurons to accelerate bone remodeling and fracture healing in mice.Journal of orthopaedic translation · 2026Article
- Neuro-Immune Axis in Trauma-Induced Heterotopic Ossification: Mechanisms and Therapeutic Implications.Cells · 2026Review
- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- Early detection of aberrant cell fate and repair using circulating progenitor cells in patients with heterotopic ossification.Nature communications · 2026Article
- Thrombospondin 1 and 2 regulate mesenchymal progenitor cell fate and matrix organization.Bone research · 2026Article
- Electroacupuncture Alleviates KOA-Induced Pain and Cartilage Degeneration via NGF/TrkA Pathway.Journal of pain research · 2026Article
- Nociceptive sensory neuron-derived NGF orchestrates a fibrotic mesenchymal stromal cell neurogenic niche to drive tendon pathological fibrosis.Nature communications · 2025Article
- Transcriptomic insights into nerve growth factor-associated appositional bone formation in the reparative zone in osteonecrosis of the femoral head.Journal of orthopaedic surgery and research · 2025Article
- Preserved fascicular architecture predicts neuroma pain: a morphometric study.Acta neuropathologica communications · 2025Article
- Single-cell sequencing uncovers sensory neuron-mediated CGRP signaling as a driver of sarcoma progression.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Understanding pain heterogeneity in osteoarthritis patients: a narrative review.Frontiers of medicine · 2025Review
- Peripheral neuronal sensitization and neurovascular remodelling in osteoarthritis pain.Nature reviews. Rheumatology · 2025Review
- p75Bone reports · 2025Article
- Divide-and-conquer strategy with engineered ossification center organoids for rapid bone healing through developmental cell recruitment.Nature communications · 2025Article
- Structurally and Functionally Adaptive Biomimetic Periosteum: Materials, Fabrication, and Construction Strategies.Exploration (Beijing, China) · 2025Review
- Article
- Selective promotion of sensory innervation-mediated immunoregulation for tissue repair.Science advances · 2025Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 7 institutions in 3 countries.
Funding
Abstract
Pain is a central feature of soft tissue trauma, which under certain contexts, results in aberrant osteochondral differentiation of tissue-specific stem cells. Here, the role of sensory nerve fibers in this abnormal cell fate decision is investigated using a severe extremity injury model in mice. Soft tissue trauma results in NGF (Nerve growth factor) expression, particularly within perivascular cell types. Consequently, NGF-responsive axonal invasion occurs which precedes osteocartilaginous differentiation. Surgical denervation impedes axonal ingrowth, with significant delays in cartilage and bone formation. Likewise, either deletion of Ngf or two complementary methods to inhibit its receptor TrkA (Tropomyosin receptor kinase A) lead to similar delays in axonal invasion and osteochondral differentiation. Mechanistically, single-cell sequencing suggests a shift from TGFβ to FGF signaling activation among pre-chondrogenic cells after denervation. Finally, analysis of human pathologic specimens and databases confirms the relevance of NGF-TrkA signaling in human disease. In sum, NGF-mediated TrkA-expressing axonal ingrowth drives abnormal osteochondral differentiation after soft tissue trauma. NGF-TrkA signaling inhibition may have dual therapeutic use in soft tissue trauma, both as an analgesic and negative regulator of aberrant stem cell differentiation.
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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.