ArticleThe American journal of pathology2017
Inhibition of Mammalian Target of Rapamycin Signaling with Rapamycin Prevents Trauma-Induced Heterotopic Ossification.
Article in The American journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- A systematic review and meta-analysis of naproxen for prevention heterotopic ossification after hip surgery.Medicine · 2019Pooled it
- Efficacy of naproxen prophylaxis for the prevention of heterotopic ossification after hip surgery: a meta-analysis.Journal of orthopaedic surgery and research · 2018Pooled it
- Heterotopic Ossification: Molecular Drivers, Subtype-Specific Mechanisms, and Translational Therapeutic Advances.Biomolecules · 2026Review
- Rapamycin reduces peritendinous fibrosis but has a limited effect on intratendinous healing in a rodent Achilles tendon injury model.Scientific reports · 2026Article
- Angiogenesis in ossification of the posterior longitudinal ligament: progress from mechanism to targeted intervention.Frontiers in cell and developmental biology · 2026Review
- Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva.Journal of Zhejiang University. Science. B · 2025Review
- Heterotopic ossification: Current developments and emerging potential therapies.Chinese medical journal · 2025Review
- Immunologic Aspects in Fibrodysplasia Ossificans Progressiva.Biomolecules · 2024Review
- Intersections of Fibrodysplasia Ossificans Progressiva and Traumatic Heterotopic Ossification.Biomolecules · 2024Review
- Systematic Identification of the Optimal Housekeeping Genes for Accurate Transcriptomic and Proteomic Profiling of Tissues following Complex Traumatic Injury.Methods and protocols · 2023Article
- Inhibition of focal adhesion kinase 2 results in a macrophage polarization shift to M2 which attenuates local and systemic inflammation and reduces heterotopic ossification after polysystem extremity trauma.Frontiers in immunology · 2023Article
- Skeletal stem cells: origins, definitions, and functions in bone development and disease.Life medicine · 2022Review
- Fifteen years' experience of radiation therapy for resected advanced heterotopic ossification following motor vehicle accidents: outcome and side effects.Journal of the Egyptian National Cancer Institute · 2022Article
- Fetuin-A is an immunomodulator and a potential therapeutic option in BMP4-dependent heterotopic ossification and associated bone mass loss.Bone research · 2022Article
- Contemporary perspectives on heterotopic ossification.JCI insight · 2022Review
- Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification.International journal of molecular sciences · 2022Review
- [Research progress of traumatic heterotopic ossification].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2022Review
- Case Report: Everolimus reduced bone turnover markers but showed no clinical benefit in a patient with severe progressive osseous heteroplasia.Frontiers in pediatrics · 2022Article
- Culture and characterization of various porcine integumentary-connective tissue-derived mesenchymal stromal cells to facilitate tissue adhesion to percutaneous metal implants.Stem cell research & therapy · 2021Article
- Rapamycin alleviates memory deficit against pentylenetetrazole-induced neural toxicity in Wistar male rats.Molecular biology reports · 2021Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
A pressing clinical need exists for 63% to 65% of combat-wounded service members and 11% to 20% of civilians who develop heterotopic ossification (HO) after blast-related extremity injury and traumatic injuries, respectively. The mammalian target of rapamycin pathway is a central cellular sensor of injury. We evaluated the prophylactic effects of rapamycin, a selective inhibitor of mammalian target of rapamycin signaling, on HO formation in a rat model of blast-related, polytraumatic extremity injury. Rapamycin was administered intraperitoneally daily for 14 days at 0.5 mg/kg or 2.5 mg/kg. Ectopic bone formation was monitored by micro-computed tomography and confirmed by histologic examination. Connective tissue progenitor cells, platelet-derived growth factor receptor-α-positive cells, and α-smooth muscle actin-positive blood vessels were assayed at postoperative day 7 by colony formation and immunofluorescence. Early gene expression changes were determined by low-density microarray. There was significant attenuation of 1) total new bone and soft tissue ectopic bone with 0.5 mg/kg (38.5% and 14.7%) and 2.5 mg/kg rapamycin (90.3% and 82.9%), respectively, 2) connective tissue progenitor cells, 3) platelet-derived growth factor receptor-α-positive cells, 4) α-smooth muscle actin-positive blood vessels, and 5) of key extracellular matrix remodeling (CD44, Col1a1, integrins), osteogenesis (Sp7, Runx2, Bmp2), inflammation (Cxcl5, 10, IL6, Ccl2), and angiogenesis (Angpt2) genes. No wound healing complications were noted. Our data demonstrate the efficacy of rapamycin in inhibiting blast trauma-induced HO by a multipronged mechanism.
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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.