ArticleJournal of vascular surgery2017
Dorsomorphin homologue 1, a highly selective small-molecule bone morphogenetic protein inhibitor, suppresses medial artery calcification.
Article in Journal of vascular surgery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- DMH1 improves palmitic acid-Induced insulin resistance in cardiomyocytes via PP2A inhibition and AKT/AMPK signaling activation.Scientific reports · 2026Article
- A genome-wide association study of imaging-defined atherosclerosis.Nature communications · 2025Article
- Article
- Two Modulators of Skeletal Development: BMPs and Proteoglycans.Journal of developmental biology · 2022Review
- Premature Vertebral Mineralization inCells · 2022Article
- Vascular Calcification: New Insights Into BMP Type I Receptor A.Frontiers in pharmacology · 2022Review
- Review
- A novel negative regulatory mechanism of Smurf2 in BMP/Smad signaling in bone.Bone research · 2020Article
- Mechanisms of calcification in Fahr disease and exposure of potential therapeutic targets.Neurology. Clinical practice · 2020Review
- Bone Morphogenetic Protein-2 in Development and Bone Homeostasis.Journal of developmental biology · 2020Review
- Bone Morphogenetic Protein-Based Therapeutic Approaches.Cold Spring Harbor perspectives in biology · 2018Review
- Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling.Scientific reports · 2018Article
- Inhibition of endo-lysosomal function exacerbates vascular calcification.Scientific reports · 2018Article
- IL-6 potentiates BMP-2-induced osteogenesis and adipogenesis via two different BMPR1A-mediated pathways.Cell death & disease · 2018Article
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5 authors at 2 institutions in 2 countries.
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Abstract
backgroundMedial artery calcification develops in diabetes, chronic kidney disease, and as part of the aging process. It is associated with increased morbidity and mortality in vascular patients. Bone morphogenetic proteins (BMPs) have previously been implicated in the initiation and progression of vascular calcification. We thus evaluated whether dorsomorphin homologue 1 (DMH1), a highly selective BMP inhibitor, could attenuate vascular calcification in vitro and in an organ culture model of medial calcification.
methodsConfluent human aortic smooth muscle cells (SMCs) were cultured in calcification medium containing 3.0 mM inorganic phosphate (Pi) for 7 days with or without DMH1. Medial calcification was assessed using an aortic organ culture model. Calcification was visualized by alizarin red S staining, and calcium concentration was assessed by an o-cresolphthalein complexone calcium assay. Osteogenic cell and vascular SMC markers were determined by Western blot, quantitative reverse transcription polymerase chain reaction, and immunohistochemical staining.
resultsDMH1 reduced Pi-induced calcium deposition in human SMCs. It also antagonized human recombinant BMP2-induced calcium accumulation. Western blot further revealed that DMH1 was able to block Pi-mediated upregulation of the osteoblast markers osterix and alkaline phosphatase and downregulation of the SMC markers smooth muscle myosin heavy chain and SM22α as well as p-Smad1/5/8, suggesting that DMH1 may regulate SMC osteogenic differentiation through the BMP/Smad1/5/8 signaling pathway. Finally, using an ex vivo aortic ring organ culture model, we observed that DMH1 reduces Pi-induced aortic medial calcification.
conclusionsThe selective BMP inhibitor DMH1 can inhibit calcium accumulation in vascular SMCs and arterial segments exposed to elevated phosphate levels. Such small molecules may have clinical utility in reducing medial artery calcification in our population of vascular patients.
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