ArticleJournal of cellular biochemistry2011
Sensory nerve induced inflammation contributes to heterotopic ossification.
Article in Journal of cellular biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Use of calcitonin in recalcitrant phantom limb pain complicated by heterotopic ossification.Pain research & managementPooled it
- Sensing the skeleton: sensorineural regulation in bone.Nature reviews. Neuroscience · 2026Review
- Neurogenic heterotopic ossification: from molecular mechanisms to clinical treatment.Journal of orthopaedic translation · 2026Review
- Brain-bone Crosstalk after Neurotrauma: Dual Effects of Traumatic Brain Injury on Skeletal Remodeling.Current osteoporosis reports · 2026Review
- Neuro-Immune Axis in Trauma-Induced Heterotopic Ossification: Mechanisms and Therapeutic Implications.Cells · 2026Review
- Heterotopic Ossification: Molecular Drivers, Subtype-Specific Mechanisms, and Translational Therapeutic Advances.Biomolecules · 2026Review
- Sensory Nerve-Derived CGRP Controls Osteoclastogenesis by Limiting Macrophage Bioenergetics in Bone Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Angiogenesis in ossification of the posterior longitudinal ligament: progress from mechanism to targeted intervention.Frontiers in cell and developmental biology · 2026Review
- Article
- Review
- Denervation‑induced NRG3 aggravates muscle heterotopic ossification via the ErbB4/PI3K/Akt signaling pathway.Molecular medicine reports · 2025Article
- Mast cell activation by NGF drives the formation of trauma-induced heterotopic ossification.JCI insight · 2024Article
- Sensory nerve EP4 facilitates heterotopic ossification by regulating angiogenesis-coupled bone formation.Journal of orthopaedic translation · 2024Article
- Pharmacologic or genetic targeting of peripheral nerves prevents peri-articular traumatic heterotopic ossification.Bone research · 2024Article
- The Role of Neuromodulation and Potential Mechanism in Regulating Heterotopic Ossification.Neurochemical research · 2024Review
- Intersections of Fibrodysplasia Ossificans Progressiva and Traumatic Heterotopic Ossification.Biomolecules · 2024Review
- Metformin alleviates genetic and traumatic heterotopic ossification by inhibiting infiltration and mitochondrial metabolism of myeloid cells.American journal of translational research · 2024Article
- Estrogen Deficiency Exacerbates Traumatic Heterotopic Ossification in Mice.Journal of inflammation research · 2024Article
- A microCT-based platform to quantify drug targeting.European radiology experimental · 2023Article
- Substance P Exacerbates the Inflammatory and Pro-osteoclastogenic Responses of Murine Osteoclasts and Osteoblasts to Staphylococcus aureus.Inflammation · 2023Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Heterotopic ossification (HO), or bone formation in soft tissues, is often the result of traumatic injury. Much evidence has linked the release of BMPs (bone morphogenetic proteins) upon injury to this process. HO was once thought to be a rare occurrence, but recent statistics from the military suggest that as many as 60% of traumatic injuries, resulting from bomb blasts, have associated HO. In this study, we attempt to define the role of peripheral nerves in this process. Since BMP2 has been shown previously to induce release of the neuroinflammatory molecules, substance P (SP) and calcitonin gene related peptide (CGRP), from peripheral, sensory neurons, we examined this process in vivo. SP and CGRP are rapidly expressed upon delivery of BMP2 and remain elevated throughout bone formation. In animals lacking functional sensory neurons (TRPV1(-/-) ), BMP2-mediated increases in SP and CGRP were suppressed as compared to the normal animals, and HO was dramatically inhibited in these deficient mice, suggesting that neuroinflammation plays a functional role. Mast cells, known to be recruited by SP and CGRP, were elevated after BMP2 induction. These mast cells were localized to the nerve structures and underwent degranulation. When degranulation was inhibited using cromolyn, HO was again reduced significantly. Immunohistochemical analysis revealed nerves expressing the stem cell markers nanog and Klf4, as well as the osteoblast marker osterix, after BMP2 induction, in mice treated with cromolyn. The data collectively suggest that BMP2 can act directly on sensory neurons to induce neurogenic inflammation, resulting in nerve remodeling and the migration/release of osteogenic and other stem cells from the nerve. Further, blocking this process significantly reduces HO, suggesting that the stem cell population contributes to bone formation.
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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.