ArticleJCI insight2018
NF-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Periprosthetic joint infection and heterotopic ossification after total hip arthroplasty: systematic review and meta-analysis.BMC musculoskeletal disorders · 2025Pooled it
- Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.Annals of medicine · 2026Article
- Clec3bBone research · 2026Article
- Precision RNAi for Fibrodysplasia Ossificans Progressiva: a combinatorial, unimolecular, allele selective approach.Research square · 2026Article
- USP24-dependent STAT2 stabilization mediates physiologic and pathologic bone formation.Cell death & disease · 2026Article
- Heterotopic Ossification: Molecular Drivers, Subtype-Specific Mechanisms, and Translational Therapeutic Advances.Biomolecules · 2026Review
- Gut microbiome-dependent IL-1 signaling is a mediator of ACVR1bioRxiv : the preprint server for biology · 2026Article
- Integrin-mediated SPP1 signaling from macrophages orchestrates extracellular matrix remodeling and chondrogenesis in heterotopic ossification.Journal of translational medicine · 2025Article
- TGF-β signaling in heterotopic ossification: the pathogenesis and the target for its treatment.Journal of orthopaedic surgery and research · 2025Review
- Medical guidelines for fibrodysplasia ossificans progressiva.JBMR plus · 2025Article
- Regenerative biologics modulating inflammation and promoting tenogenesis in equine superficial digital flexor tendonitis: from molecular pathways to clinical translation.Irish veterinary journal · 2025Review
- Triptolide Attenuates Traumatic Heterotopic Ossification via Modulation of Inflammatory and Differentiation Pathways: Implications for Biochemical Toxicology.Journal of biochemical and molecular toxicology · 2025Article
- Momelotinib Is Effective in Treatment for VEXAS Syndrome: Two Cases Within the AGMT Austrian Myeloid Registry.European journal of haematology · 2025Article
- Article
- Macrophage Polarization in Heterotopic Ossification: Inflammation, Osteogenesis, and Emerging Therapeutic Targets.International journal of molecular sciences · 2025Review
- Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva.Journal of Zhejiang University. Science. B · 2025Review
- All Restricted Spines are not Spondyloarthritis: Fibrodysplasia Ossificans Progressiva (FOP) in Monozygotic Twins presenting to Rheumatology Clinic.Mediterranean journal of rheumatology · 2025Article
- BMP-9 mediates fibroproliferation in fibrodysplasia ossificans progressiva through TGF-β signaling.EMBO molecular medicine · 2025Article
- Review
- Fibroblasts in heterotopic ossification: mechanisms and therapeutic targets.International journal of biological sciences · 2025Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundInflammation helps regulate normal growth and tissue repair. Although bone morphogenetic proteins (BMPs) and inflammation are known contributors to abnormal bone formation, how these pathways interact in ossification remains unclear.
methodsWe examined this potential link in patients with fibrodysplasia ossificans progressiva (FOP), a genetic condition of progressive heterotopic ossification caused by activating mutations in the Activin A type I receptor (ACVR1/ALK2). FOP patients show exquisite sensitivity to trauma, suggesting that BMP pathway activation may alter immune responses. We studied primary blood, monocyte, and macrophage samples from control and FOP subjects using multiplex cytokine, gene expression, and protein analyses; examined CD14+ primary monocyte and macrophage responses to TLR ligands; and assayed BMP, TGF-β activated kinase 1 (TAK1), and NF-κB pathways.
resultsFOP subjects at baseline without clinically evident heterotopic ossification showed increased serum IL-3, IL-7, IL-8, and IL-10. CD14+ primary monocytes treated with the TLR4 activator LPS showed increased CCL5, CCR7, and CXCL10; abnormal cytokine/chemokine secretion; and prolonged activation of the NF-κB pathway. FOP macrophages derived from primary monocytes also showed abnormal cytokine/chemokine secretion, increased TGF-β production, and p38MAPK activation. Surprisingly, SMAD phosphorylation was not significantly changed in the FOP monocytes/macrophages.
conclusionsAbnormal ACVR1 activity causes a proinflammatory state via increased NF-κB and p38MAPK activity. Similar changes may contribute to other types of heterotopic ossification, such as in scleroderma and dermatomyositis; after trauma; or with recombinant BMP-induced bone fusion. Our findings suggest that chronic antiinflammatory treatment may be useful for heterotopic ossification.
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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.