ArticleThe Journal of clinical investigation2017
Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.
- When Limb Surgery Has Become the Only Life-Saving Therapy in FOP: A Case Report and Systematic Review of the Literature.Frontiers in endocrinology · 2020Pooled it
- Heterotopic Ossification: Molecular Drivers, Subtype-Specific Mechanisms, and Translational Therapeutic Advances.Biomolecules · 2026Review
- Fibrodysplasia ossificans progressiva: genetic and clinical characterization in a cohort of Polish patients and review of potential therapies.Journal of applied genetics · 2026Review
- TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease.Bone research · 2026Review
- Assessing rare disease understanding: a novel disease readiness level framework.Orphanet journal of rare diseases · 2025Article
- An inducible knock-in mouse model of fibrodysplasia ossificans progressiva shows spontaneous formation of heterotopic ossification.JBMR plus · 2025Article
- Macrophage Polarization in Heterotopic Ossification: Inflammation, Osteogenesis, and Emerging Therapeutic Targets.International journal of molecular sciences · 2025Review
- Article
- Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva.Journal of Zhejiang University. Science. B · 2025Review
- Interplay between ALK2Cell death discovery · 2025Article
- Induced Mesenchymal Stem Cells: An Emerging Source for Regenerative Medicine Applications.Journal of clinical medicine · 2025Review
- Activin A affects colorectal cancer progression and immunomodulation in a stage dependent manner.Scientific reports · 2025Article
- All Restricted Spines are not Spondyloarthritis: Fibrodysplasia Ossificans Progressiva (FOP) in Monozygotic Twins presenting to Rheumatology Clinic.Mediterranean journal of rheumatology · 2025Article
- Hydroxycitric acid reconstructs damaged articular cartilages by modifying the metabolic cascade in chondrogenic cells.Osteoarthritis and cartilage open · 2025Article
- FOP: From Biomolecules to Hope.Biomolecules · 2025Article
- BMP-9 mediates fibroproliferation in fibrodysplasia ossificans progressiva through TGF-β signaling.EMBO molecular medicine · 2025Article
- Signaling Dynamics in Osteogenesis: Unraveling Therapeutic Targets for Bone Generation.Current drug targets · 2025Review
- Targeting to BMP9 to restrain flare-up of fibrodysplasia ossificans progressiva.EMBO molecular medicine · 2025Article
- Global Knowledge Map and Emerging Research Trends in Induced Pluripotent Stem Cells and Hereditary Diseases: A CiteSpace-based Visualization and Analysis.Stem cell reviews and reports · 2025Review
- Morpholino-Mediated Exon Skipping Targeting Human ACVR1/ALK2 for Fibrodysplasia Ossificans Progressiva.Methods in molecular biology (Clifton, N.J.) · 2025Article
46 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
No grant is acknowledged in the PubMed record.
Abstract
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed. To this end, we developed a high-throughput screening (HTS) system using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) to identify pivotal pathways in enhanced chondrogenesis that are initiated by Activin-A. In a screen of 6,809 small-molecule compounds, we identified mTOR signaling as a critical pathway for the aberrant chondrogenesis of mesenchymal stromal cells derived from FOP-iPSCs (FOP-iMSCs). Two different HO mouse models, an FOP model mouse expressing FOP-ACVR1 and an FOP-iPSC-based HO model mouse, revealed critical roles for mTOR signaling in vivo. Moreover, we identified ENPP2, an enzyme that generates lysophosphatidic acid, as a linker of FOP-ACVR1 and mTOR signaling in chondrogenesis. These results uncovered the crucial role of the Activin-A/FOP-ACVR1/ENPP2/mTOR axis in FOP pathogenesis.
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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.