ArticleDisease models & mechanisms2016
High-throughput screening for modulators of ACVR1 transcription: discovery of potential therapeutics for fibrodysplasia ossificans progressiva.
Article in Disease models & mechanisms, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 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
23 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Oxidative phosphorylation is a pivotal therapeutic target of fibrodysplasia ossificans progressiva.Life science alliance · 2024Article
- Berberine and aspirin prevent traumatic heterotopic ossification by inhibition of BMP signalling pathway and osteogenic differentiation.Journal of cellular and molecular medicine · 2023Article
- Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification.International journal of molecular sciences · 2022Review
- Two Modulators of Skeletal Development: BMPs and Proteoglycans.Journal of developmental biology · 2022Review
- [Research progress of traumatic heterotopic ossification].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2022Review
- A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene.Molecular genetics & genomic medicine · 2021Article
- Genetic and Acquired Heterotopic Ossification: A Translational Tale of Mice and Men.Biomedicines · 2020Review
- OGT-Mediated KEAP1 Glycosylation Accelerates NRF2 Degradation Leading to High Phosphate-Induced Vascular Calcification in Chronic Kidney Disease.Frontiers in physiology · 2020Article
- MicroRNA-410 participates in the pathological process of postmenopausal osteoporosis by downregulating bone morphogenetic protein-2.Experimental and therapeutic medicine · 2019Article
- Targeting heterotopic ossification by inhibiting activin receptor‑like kinase 2 function (Review).Molecular medicine reports · 2019Review
- Severe Heterotopic Ossification in the Skeletal Muscle and Endothelial Cells Recruitment to Chondrogenesis Are Enhanced by Monocyte/Macrophage Depletion.Frontiers in immunology · 2019Article
- Application ofFrontiers in pharmacology · 2019Article
- Bone morphogenetic protein receptor signal transduction in human disease.The Journal of pathology · 2019Review
- An mTOR Signaling Modulator Suppressed Heterotopic Ossification of Fibrodysplasia Ossificans Progressiva.Stem cell reports · 2018Article
- MicroRNA-384 inhibits the progression of breast cancer by targeting ACVR1.Oncology reports · 2018Article
- The Horizon of a Therapy for Rare Genetic Diseases: A "Druggable" Future for Fibrodysplasia Ossificans Progressiva.International journal of molecular sciences · 2018Review
- AMPK downregulates ALK2 via increasing the interaction between Smurf1 and Smad6, leading to inhibition of osteogenic differentiation.Biochimica et biophysica acta. Molecular cell research · 2017Article
- Fibrodysplasia ossificans progressiva: Basic understanding and experimental models.Intractable & rare diseases research · 2017Review
- Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva.The Journal of clinical investigation · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
The ACVR1 gene encodes a type I receptor of bone morphogenetic proteins (BMPs). Activating mutations in ACVR1 are responsible for fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by congenital toe malformation and progressive heterotopic endochondral ossification leading to severe and cumulative disability. Until now, no therapy has been available to prevent soft-tissue swelling (flare-ups) that trigger the ossification process. With the aim of finding a new therapeutic strategy for FOP, we developed a high-throughput screening (HTS) assay to identify inhibitors of ACVR1 gene expression among drugs already approved for the therapy of other diseases. The screening, based on an ACVR1 promoter assay, was followed by an in vitro and in vivo test to validate and characterize candidate molecules. Among compounds that modulate the ACVR1 promoter activity, we selected the one showing the highest inhibitory effect, dipyridamole, a drug that is currently used as a platelet anti-aggregant. The inhibitory effect was detectable on ACVR1 gene expression, on the whole Smad-dependent BMP signaling pathway, and on chondrogenic and osteogenic differentiation processes by in vitro cellular assays. Moreover, dipyridamole reduced the process of heterotopic bone formation in vivo Our drug repositioning strategy has led to the identification of dipyridamole as a possible therapeutic tool for the treatment of FOP. Furthermore, our study has also defined a pipeline of assays that will be useful for the evaluation of other pharmacological inhibitors of heterotopic ossification.
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.