ArticleJCI insight2022
Macrophage TGF-β signaling is critical for wound healing with heterotopic ossification after trauma.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed.
- Immunomodulatory cytoskeleton of bionic periosteum affects mitochondrial dynamics to promote osteogenesis.Bioactive materials · 2026Article
- Regenerative macrophages enhance stem cell-derived β cell function and engraftment.Science advances · 2026Article
- Heterotopic Ossification: Molecular Drivers, Subtype-Specific Mechanisms, and Translational Therapeutic Advances.Biomolecules · 2026Review
- Immunometabolism of macrophages in the bone microenvironment: a new perspective for bone healing therapy.Journal of advanced research · 2026Review
- Targeting the CMKLR1-Mediated Signaling Rebalances Immunometabolism State in Middle-Age Testicular Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TGF-β-induced fibrotic scar formation limits recovery of spinal cord injury.Bone research · 2026Article
- M2 macrophages promote heterotopic ossification through MSX2 binding to LEF1-mediated endothelial-mesenchymal transition.Stem cell research & therapy · 2026Article
- Thrombospondin 1 and 2 regulate mesenchymal progenitor cell fate and matrix organization.Bone research · 2026Article
- Macrophages on demand: How tissue trauma shapes their role.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2026Review
- Macrophages and TGFB signaling regulate fibrosis in theAmerican journal of physiology. Renal physiology · 2026Article
- An immunomodulatory decellularized pulp matrix hydrogel promotes vascularized dental pulp regeneration through angiogenic-odontogenic coupling.Regenerative biomaterials · 2026Article
- Targeting macrophage-mediated TGF-β/BMP signaling in ankylosing spondylitis: from inflammation to pathological bone formation.Frontiers in immunology · 2026Review
- Short-term cigarette smoke exposure aggravates oxidative stress and airway inflammation induced by lipopolysaccharides.Frontiers in physiology · 2026Article
- The immune dysregulation of fibrosis: insights into immune-fibrotic crosstalk and potential therapeutic targets.Frontiers in immunology · 2026Review
- TGF-β signaling in heterotopic ossification: the pathogenesis and the target for its treatment.Journal of orthopaedic surgery and research · 2025Review
- Elucidating the Mechanism of Radiation Therapy on Mesenchymal Cell Fate in Preventing Heterotopic Ossification.Annals of surgery · 2025Article
- 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
- Recent advancement in molecular pathways and receptor targeting using natural products for wound healing activity.Inflammopharmacology · 2025Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
Abstract
Transforming growth factor-β1 (TGF-β1) plays a central role in normal and aberrant wound healing, but the precise mechanism in the local environment remains elusive. Here, using a mouse model of aberrant wound healing resulting in heterotopic ossification (HO) after traumatic injury, we find autocrine TGF-β1 signaling in macrophages, and not mesenchymal stem/progenitor cells, is critical in HO formation. In-depth single-cell transcriptomic and epigenomic analyses in combination with immunostaining of cells from the injury site demonstrated increased TGF-β1 signaling in early infiltrating macrophages, with open chromatin regions in TGF-β1-stimulated genes at binding sites specific for transcription factors of activated TGF-β1 (SMAD2/3). Genetic deletion of TGF-β1 receptor type 1 (Tgfbr1; Alk5), in macrophages, resulted in increased HO, with a trend toward decreased tendinous HO. To bypass the effect seen by altering the receptor, we administered a systemic treatment with TGF-β1/3 ligand trap TGF-βRII-Fc, which resulted in decreased HO formation and a delay in macrophage infiltration to the injury site. Overall, our data support the role of the TGF-β1/ALK5 signaling pathway in HO.
Indexed as
Identifiers
What OpenQuestion holds
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.