ArticleScience signaling2016
Increased activity of TNAP compensates for reduced adenosine production and promotes ectopic calcification in the genetic disease ACDC.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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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
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Who cites it
57 citing papers in PubMed, 84 citations in OpenAlex.
- Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC).Vascular medicine (London, England) · 2024Trial
- Phase I studies of the safety, tolerability, pharmacokinetics, and pharmacodynamics of DS-1211, a tissue-nonspecific alkaline phosphatase inhibitor.Clinical and translational science · 2022Trial
- Impaired angiogenesis and extracellular matrix metabolism in autosomal-dominant hyper-IgE syndrome.The Journal of clinical investigation · 2020Trial
- Purinergic signaling modulates endothelial-to-mesenchymal transition in human aortic valve endothelial cells.BBA advances · 2026Article
- Medial arterial calcification in ageing and disease: current evidence and knowledge gaps.European heart journal · 2025Review
- Targeting adenosine 2A receptor signaling suppresses vascular calcification by restraining smooth muscle osteogenic differentiation.Pharmacological research · 2025Article
- A Fragile Phosphate/Pyrophosphate Balance: From Essential Mineralization to Rare Calcifying Diseases.Current osteoporosis reports · 2025Review
- Rapamycin reduces mineral density and promotes beneficial vascular remodeling in a murine model of severe medial arterial calcification.American journal of physiology. Heart and circulatory physiology · 2025Article
- Phosphate in Physiological and Pathological Mineralization: Important yet Often Unheeded.MedComm · 2025Review
- Considerations on the Development of Therapeutics in Vascular Calcification.Journal of cardiovascular development and disease · 2025Review
- Rapamycin Reduces Mineral Density and Promotes Beneficial Vascular Remodeling in a Murine Model of Severe Medial Arterial Calcification.bioRxiv : the preprint server for biology · 2025Article
- Adenosine metabolism and receptors in aging of the skin, musculoskeletal, immune and cardiovascular systems.Ageing research reviews · 2025Review
- Non-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease.Circulation research · 2025Article
- Metabolites and metabolism in vascular calcification: links between adenosine signaling and the methionine cycle.American journal of physiology. Heart and circulatory physiology · 2024Review
- Establishment of a human induced pluripotent stem cell line (NIHTVBi031-A) derived from a COPA syndrome patient with a heterozygous p.Ala239Pro mutation.Stem cell research · 2024Article
- Aging Two-Step: SOX9's Influence on Vascular Stiffness and Senescence.Circulation research · 2024Article
- Role of the extracellular ATP/pyrophosphate metabolism cycle in vascular calcification.Purinergic signalling · 2023Review
- Extracellular adenosine signaling in bone health and disease.Current opinion in pharmacology · 2023Review
- An Alternate Explanation.The New England journal of medicine · 2023Article
- Ecto-5'-nucleotidase (Nt5e/CD73)-mediated adenosine signaling attenuates TGFβ-2 induced elastin and cellular contraction.American journal of physiology. Cell physiology · 2023Article
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
ACDC (arterial calcification due to deficiency of CD73) is an autosomal recessive disease resulting from loss-of-function mutations in NT5E, which encodes CD73, a 5'-ectonucleotidase that converts extracellular adenosine monophosphate to adenosine. ACDC patients display progressive calcification of lower extremity arteries, causing limb ischemia. Tissue-nonspecific alkaline phosphatase (TNAP), which converts pyrophosphate (PPi) to inorganic phosphate (Pi), and extracellular purine metabolism play important roles in other inherited forms of vascular calcification. Compared to cells from healthy subjects, induced pluripotent stem cell-derived mesenchymal stromal cells (iMSCs) from ACDC patients displayed accelerated calcification and increased TNAP activity when cultured under conditions that promote osteogenesis. TNAP activity generated adenosine in iMSCs derived from ACDC patients but not in iMSCs from control subjects, which have CD73. In response to osteogenic stimulation, ACDC patient-derived iMSCs had decreased amounts of the TNAP substrate PPi, an inhibitor of extracellular matrix calcification, and exhibited increased activation of AKT, mechanistic target of rapamycin (mTOR), and the 70-kDa ribosomal protein S6 kinase (p70S6K), a pathway that promotes calcification. In vivo, teratomas derived from ACDC patient cells showed extensive calcification and increased TNAP activity. Treating mice bearing these teratomas with an A2b adenosine receptor agonist, the mTOR inhibitor rapamycin, or the bisphosphonate etidronate reduced calcification. These results show that an increase of TNAP activity in ACDC contributes to ectopic calcification by disrupting the extracellular balance of PPi and Pi and identify potential therapeutic targets for ACDC.
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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.