ArticleLaboratory investigation; a journal of technical methods and pathology2020
Macrophage-derived neurotrophin-3 promotes heterotopic ossification in rats.
Article in Laboratory investigation; a journal of technical methods and pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.Annals of medicine · 2026Article
- Article
- Tendon stem/progenitor cells in heterotopic ossification: functional regulation, molecular mechanisms and targeted therapeutic strategies.Journal of orthopaedic translation · 2026Review
- Neurogenic heterotopic ossification: from molecular mechanisms to clinical treatment.Journal of orthopaedic translation · 2026Review
- The IL-1β/NETs/AIM2 axis participates in the formation of trauma-induced heterotopic ossification by orchestrating crosstalk between neutrophils and macrophages.Journal of advanced research · 2026Article
- The Role of Phagocytic Cells in the Achilles Tendon.International journal of molecular sciences · 2026Review
- When Bone Forms Where It Shouldn't: Heterotopic Ossification in Muscle Injury and Disease.International journal of molecular sciences · 2025Review
- A Procedural Overview of the Involvement of Small Molecules in the Nervous System in the Regulation of Bone Healing.International journal of nanomedicine · 2025Review
- Mast cell activation by NGF drives the formation of trauma-induced heterotopic ossification.JCI insight · 2024Article
- The Role of Neuromodulation and Potential Mechanism in Regulating Heterotopic Ossification.Neurochemical research · 2024Review
- Calcified apoptotic vesicles from PROCRJournal of extracellular vesicles · 2024Article
- Immunologic Aspects in Fibrodysplasia Ossificans Progressiva.Biomolecules · 2024Review
- M1 macrophage-derived oncostatin M induces osteogenic differentiation of ligamentum flavum cells through the JAK2/STAT3 pathway.JOR spine · 2024Article
- Meniscus repair via collagen matrix wrapping and bone marrow injection: clinical and biomolecular study.International orthopaedics · 2023Article
- Inhibition of NF-κB Signaling-Mediated Crosstalk Between Macrophages and Preosteoblasts by Metformin Alleviates Trauma-Induced Heterotopic Ossification.Inflammation · 2023Article
- Bioactive semaphorin 3A promotes sequential formation of sensory nerve and type H vessels duringFrontiers in bioengineering and biotechnology · 2023Article
- Hedgehog Signalling Contributes to Trauma-Induced Tendon Heterotopic Ossification and Regulates Osteogenesis through Antioxidant Pathway in Tendon-Derived Stem Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Roles of Oxidative Stress in Acute Tendon Injury and Degenerative Tendinopathy-A Target for Intervention.International journal of molecular sciences · 2022Review
- Macrophages in heterotopic ossification: from mechanisms to therapy.NPJ Regenerative medicine · 2021Review
- Quercetin Attenuates Trauma-Induced Heterotopic Ossification by Tuning Immune Cell Infiltration and Related Inflammatory Insult.Frontiers in immunology · 2021Article
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8 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Heterotopic ossification (HO) is a debilitating condition that results from traumatic injuries or genetic diseases, for which the underlying mechanisms remain unclear. Recently, we have demonstrated the expression of neurotrophin-3 (NT-3) and its role in promoting HO formation via mediating endothelial-mesenchymal transition (EndMT) of vascular endothelial cells. The current study investigated the role of NT-3 on the surrounding mesenchymal cells and its potential origin throughout HO formation at injured Achilles tendons in rats. We used an Achilles tenotomy to induce HO formation in vivo and cultured primary tendon-derived stem cells (TDSCs) to investigate the underlying mechanisms mediating the osteogenesis in vitro. Furthermore, RAW264.7 cells were employed to identify the origin of NT-3. The mRNA levels of NGF, BDNF, NT-3, and NT-4 and their tyrosine protein kinase (Trk) receptors as well as p75 receptor were elevated at injury sites. NT-3 and TrkC showed the highest induction. Neutralization of the NT-3-induced effects by the pan-Trk inhibitor GNF5837 reduced the expression of bone/cartilage-related genes while injection of NT-3 promoted HO formation with elevated mRNA of bone/cartilage-related markers at injured sites. In vitro, NT-3 accelerated osteogenic differentiation and mineralization of TDSCs through activation of the ERK1/2 and PI3K/Akt signaling pathways. Moreover, the colocalization of NT-3 and macrophages, including M1 and M2 macrophages, was observed in injured sites throughout HO formation, and in vitro studies demonstrated that activated macrophages mediated the secretion of NT-3. In addition, an increasing concentration of serum or supernatant NT-3 was observed both in vivo and in vitro. Depletion of macrophages with clodronate-loaded liposomes reduced HO formation as well as secretion and mRNA expression of NT-3. Our study suggests that macrophage-derived NT-3 may promote HO formation and osteogenesis of TDSCs via the ERK1/2 and PI3K/Akt signaling pathways, which may provide new insights for the therapeutic directions of HO in the future.
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