ArticleBone research2019
Inhibition of immune checkpoints prevents injury-induced heterotopic ossification.
Article in Bone research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
21 citing papers in PubMed, 33 citations in OpenAlex.
- Brain-bone Crosstalk after Neurotrauma: Dual Effects of Traumatic Brain Injury on Skeletal Remodeling.Current osteoporosis reports · 2026Review
- PRMT6 is required for initiating and amplifying macrophage-induced inflammation in heterotopic ossification by increasing CCL2 expression.Bone research · 2026Article
- Fibrodysplasia ossificans progressiva: genetic and clinical characterization in a cohort of Polish patients and review of potential therapies.Journal of applied genetics · 2026Review
- Single cell RNA-seq analysis associates Osm signaling in macrophages with osteogenic differentiation during heterotopic ossification.Journal of orthopaedic surgery and research · 2025Article
- Pak4-mediated crosstalk between necroptotic macrophages and tendon stem/progenitor cells contributes to traumatic heterotopic ossification formation.Bone research · 2025Article
- 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
- Macrophage Polarization in Heterotopic Ossification: Inflammation, Osteogenesis, and Emerging Therapeutic Targets.International journal of molecular sciences · 2025Review
- Heterotopic ossification: Current developments and emerging potential therapies.Chinese medical journal · 2025Review
- 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
- Article
- Calcified apoptotic vesicles from PROCRJournal of extracellular vesicles · 2024Article
- Metformin alleviates genetic and traumatic heterotopic ossification by inhibiting infiltration and mitochondrial metabolism of myeloid cells.American journal of translational research · 2024Article
- Review
- Inhibition of NF-κB Signaling-Mediated Crosstalk Between Macrophages and Preosteoblasts by Metformin Alleviates Trauma-Induced Heterotopic Ossification.Inflammation · 2023Article
- Fetuin-A is an immunomodulator and a potential therapeutic option in BMP4-dependent heterotopic ossification and associated bone mass loss.Bone research · 2022Article
- Macrophages in heterotopic ossification: from mechanisms to therapy.NPJ Regenerative medicine · 2021Review
- Burn-induced heterotopic ossification from incidence to therapy: key signaling pathways underlying ectopic bone formation.Cellular & molecular biology letters · 2021Review
- Heterotopic ossification in mice overexpressing Bmp2 in Tie2+ lineages.Cell death & disease · 2021Article
- Current Understanding of Osteoimmunology in Certain Osteoimmune Diseases.Frontiers in cell and developmental biology · 2021Review
- Quercetin Attenuates Trauma-Induced Heterotopic Ossification by Tuning Immune Cell Infiltration and Related Inflammatory Insult.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
Abstract
Heterotopic ossification (HO), true bone formation in soft tissue, is closely associated with abnormal injury/immune responses. We hypothesized that a key underlying mechanism of HO might be injury-induced dysregulation of immune checkpoint proteins (ICs). We found that the earliest stages of HO are characterized by enhanced infiltration of polarized macrophages into sites of minor injuries in an animal model of HO. The non-specific immune suppressants, Rapamycin and Ebselen, prevented HO providing evidence of the central role of the immune responses. We examined the expression pattern of ICs and found that they are dysregulated in HO lesions. More importantly, loss of function of inhibitory ICs (including PD1, PD-L1, and CD152) markedly inhibited HO, whereas loss of function of stimulatory ICs (including CD40L and OX-40L) facilitated HO. These findings suggest that IC inhibitors may provide a therapeutic approach to prevent or limit the extent of HO.
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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.