ArticleThe Journal of surgical research2016
The role of the adaptive immune system in burn-induced heterotopic ossification and mesenchymal cell osteogenic differentiation.
Article in The Journal of surgical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- The alpha and the omega (6 lipids): discovering dietary drivers of heterotopic ossification.The Journal of clinical investigation · 2026Article
- Association and predictive value of systemic immune-inflammation index and body mass index in cervical ossification of the posterior longitudinal ligament.Frontiers in molecular biosciences · 2026Article
- Identification and validation of core oxidative phosphorylation-related genes as biomarkers for immune response and diagnosis in burn injury.Frontiers in immunology · 2026Article
- Single cell RNA-seq analysis associates Osm signaling in macrophages with osteogenic differentiation during heterotopic ossification.Journal of orthopaedic surgery and research · 2025Article
- When Bone Forms Where It Shouldn't: Heterotopic Ossification in Muscle Injury and Disease.International journal of molecular sciences · 2025Review
- Deciphering the Regulatory Networks of the Migrasome-Associated Cell Subpopulation in Heterotopic Ossification via Multi-Omics Analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single-Cell Level.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Immunologic Aspects in Fibrodysplasia Ossificans Progressiva.Biomolecules · 2024Review
- Metformin alleviates genetic and traumatic heterotopic ossification by inhibiting infiltration and mitochondrial metabolism of myeloid cells.American journal of translational research · 2024Article
- Neuron-to-vessel signaling is a required feature of aberrant stem cell commitment after soft tissue trauma.Bone research · 2022Article
- High Systemic Immune-Inflammation Index and Body Mass Index Are Independent Risk Factors of the Thoracic Ossification of the Ligamentum Flavum.Mediators of inflammation · 2022Article
- Lymphocytes Are Not Required for Neurogenic Heterotopic Ossification Development after Spinal Cord Injury.Neurotrauma reports · 2022Article
- Burn-induced heterotopic ossification from incidence to therapy: key signaling pathways underlying ectopic bone formation.Cellular & molecular biology letters · 2021Review
- Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway.Nature communications · 2021Article
- Article
- Inflammation in Fibrodysplasia Ossificans Progressiva and Other Forms of Heterotopic Ossification.Current osteoporosis reports · 2019Review
- Heterotopic Ossification: A Comprehensive Review.JBMR plus · 2019Review
- Inhibition of immune checkpoints prevents injury-induced heterotopic ossification.Bone research · 2019Article
- Risk of pneumonia in patients with burn injury: a population-based cohort study.Clinical epidemiology · 2018Article
- Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHeterotopic ossification (HO) is the pathologic process of extraskeletal bone formation. Although the exact etiology remains unknown, inflammation appears to catalyze disease progression. The goal of this study is to determine the impact of the adaptive immune system on HO.
methodsHO was induced in 8-wk-old control C57BL/6 and immunocompromised Rag1tm1Mom (Rag1 KO) male mice deficient in B- and T-lymphocytes via combined Achilles tenotomy and burn injury. Microcomputed tomography quantified the extent of HO formation at the tenotomy site. Adipose-derived mesenchymal stem cells were harvested to evaluate osteogenic differentiation potential.
resultsAreas of developing HO demonstrated substantial enrichment of CD45 + leukocytes at 3 wk after injury. HO from Rag1 KO mice was substantially less mature with foci of cartilage and disorganized trabecular bone present 12 wk after injury. Rag1 KO mice formed 60% less bone compared to immunocompetent controls (4.67 ± 1.5 mm versus 7.76 ± 0.65 mm; P = 0.001). Tartrate-resistant acid phosphatase staining and immunofluorescent analysis of osteoprotegerin and nuclear factor kappa-light-chain-enhancer of activated B cells demonstrated no appreciable difference in osteoclast number or activation. Alizarin red staining in vitro demonstrated a significant decrease in osteogenic potential in immunocompromised mice compared to controls (29.1 ± 0.54 mm versus 12.1 ± 0.14 mm; P < 0.001).
conclusionsWe demonstrate a prominent role for the adaptive immune system in the development of HO. In the absence of mature B- and T-lymphocytes, HO growth and development are attenuated. Furthermore, we demonstrate that mesenchymal populations from B- and T-cell deficient mice are inherently less osteogenic. This study identifies a potential therapeutic role for modulation of the adaptive immune system in the treatment of HO.
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