ArticleClinical orthopaedics and related research2015
Early Characterization of Blast-related Heterotopic Ossification in a Rat Model.
Article in Clinical orthopaedics and related research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Neuro-Immune Axis in Trauma-Induced Heterotopic Ossification: Mechanisms and Therapeutic Implications.Cells · 2026Review
- Review
- Denervation‑induced NRG3 aggravates muscle heterotopic ossification via the ErbB4/PI3K/Akt signaling pathway.Molecular medicine reports · 2025Article
- From inflammation to bone formation: the intricate role of neutrophils in skeletal muscle injury and traumatic heterotopic ossification.Experimental & molecular medicine · 2024Review
- Systematic Identification of the Optimal Housekeeping Genes for Accurate Transcriptomic and Proteomic Profiling of Tissues following Complex Traumatic Injury.Methods and protocols · 2023Article
- Tourniquet use following blast-associated complex lower limb injury and traumatic amputation promotes end organ dysfunction and amplified heterotopic ossification formation.Journal of orthopaedic surgery and research · 2022Article
- Key early proinflammatory signaling molecules encapsulated within circulating exosomes following traumatic injury.Journal of inflammation (London, England) · 2022Article
- Macrophages in heterotopic ossification: from mechanisms to therapy.NPJ Regenerative medicine · 2021Review
- High Frequency Spectral Ultrasound Imaging Detects Early Heterotopic Ossification in Rodents.Stem cells and development · 2021Article
- Review
- Saracatinib is an efficacious clinical candidate for fibrodysplasia ossificans progressiva.JCI insight · 2021Article
- Development of a rodent high-energy blast injury model for investigating conditions associated with traumatic amputations.Bone & joint research · 2021Article
- BMP Ligand Trap ALK3-Fc Attenuates Osteogenesis and Heterotopic Ossification in Blast-Related Lower Extremity Trauma.Stem cells and development · 2021Article
- Neurological heterotopic ossification: novel mechanisms, prognostic biomarkers and prophylactic therapies.Bone research · 2020Review
- When the Nervous System Turns Skeletal Muscles into Bones: How to Solve the Conundrum of Neurogenic Heterotopic Ossification.Current osteoporosis reports · 2020Review
- Article
- Heterotopic ossification of tendon and ligament.Journal of cellular and molecular medicine · 2020Review
- Methods for the reliable induction of heterotopic ossification in the conditionalJournal of musculoskeletal & neuronal interactions · 2020Article
- Inflammation in Fibrodysplasia Ossificans Progressiva and Other Forms of Heterotopic Ossification.Current osteoporosis reports · 2019Review
- Elevated BMP and Mechanical Signaling Through YAP1/RhoA Poises FOP Mesenchymal Progenitors for Osteogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHeterotopic ossification (HO) affects the majority of combat-related lower extremity wounds involving severe fracture and amputation. Defining the timing of early osteogenic-related genes may help identify candidate prophylactic agents and guide the timing of prophylactic therapy after blast and other combat-related extremity injuries. QUESTIONS/PURPOSES: Using a recently developed animal model of combat-related HO, we sought to determine (1) the timing of early chondrogenesis, cartilage formation, and radiographic ectopic bone development; and (2) the early cartilage and bone-related gene and protein patterns in traumatized soft tissue.
methodsWe used an established rat HO model consisting of blast exposure, controlled femur fracture, crush injury, and transfemoral amputation through the zone of injury. Postoperatively, rats were euthanized on Days 3 to 28. We assessed evidence of early ectopic bone formation by micro-CT and histology and performed proteomic and gene expression analysis.
resultsAll rats showed radiographic evidence of HO within 28 days. Key chondrogenic (collagen type I alpha 1 [COL1α1], p = 0.016) and osteogenic-related genes (Runt-related transcription factor 2 [RUNX-2], p = 0.029; osteoclacin [OCN], p = 0.032; phosphate-regulating neutral endopeptidase, X-linked [PHEX], p = 0.0290, and POU domain class 5 transcription factor [POU5F], p = 0.016) and proteins (Noggin [NOG], p = 0.04, OCN, p = 0.02, RUNX- 2, p = 0.04, and substance P-1 [SP-1], p = 0.01) in the injured soft tissue, normalized to the contralateral limb and/or sham-treated naïve rats, increased on Days 3 to 14 postinjury. By 14 days, foci of hypertrophic chondrocytes, hyaline cartilage, and woven bone were present in the soft tissue surrounding the amputation site.
conclusionsWe found that genes that regulate early chondrogenic and osteogenic signaling and bone development (COL1α1, RUNX-2, OCN, PHEX, and POU5F1) are induced early during the tissue reparative/healing phase in a rat model simulating a combat-related extremity injury. CLINICAL RELEVANCE: The ability to correlate molecular events with histologic and morphologic changes will assist researchers and clinicians to understand HO and hence formulate therapeutic interventions.
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