ArticleBone2020
Pharmacological TNAP inhibition efficiently inhibits arterial media calcification in a warfarin rat model but deserves careful consideration of potential physiological bone formation/mineralization impairment.
Article in Bone, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 25 citations in OpenAlex.
- Considerations on the Development of Therapeutics in Vascular Calcification.Journal of cardiovascular development and disease · 2025Review
- Hexasodium Fytate (SNF472 or CSL525) Inhibits Ectopic Calcification in Various Pseudoxanthoma Elasticum and Calcinosis Cutis Animal Models.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Mechanisms of Cardiovascular Calcification and Experimental Models: Impact of Vitamin K Antagonists.Journal of clinical medicine · 2024Review
- Vascular calcification: from the perspective of crosstalk.Molecular biomedicine · 2023Review
- A DNA-encoded chemical library based on chiral 4-amino-proline enables stereospecific isozyme-selective protein recognition.Nature chemistry · 2023Article
- Frontiers in Bone Metabolism and Disorder in Chronic Kidney Disease.Metabolites · 2023Article
- A Proteomic Screen to Unravel the Molecular Pathways Associated with Warfarin-Induced or TNAP-Inhibited Arterial Calcification in Rats.International journal of molecular sciences · 2023Article
- Review
- Warfarin-Induced Calcification: Potential Prevention and Treatment Strategies.Reviews in cardiovascular medicine · 2022Review
- Inhibition of the DNA Damage Response Attenuates Ectopic Calcification in Pseudoxanthoma Elasticum.The Journal of investigative dermatology · 2022Article
- New Therapeutics Targeting Arterial Media Calcification: Friend or Foe for Bone Mineralization?Metabolites · 2022Review
- Review
- Uremic Toxin Lanthionine Induces Endothelial Cell Mineralization In Vitro.Biomedicines · 2022Article
- TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body.Cardiovascular research · 2022Review
- The Physiological and Pathological Role of Tissue Nonspecific Alkaline Phosphatase beyond Mineralization.Biomolecules · 2021Review
- Biomolecules Orchestrating Cardiovascular Calcification.Biomolecules · 2021Review
- Article
- Cutaneous and Vascular Deposits of 18F-NaF by PET/CT in the Follow-Up of Patients with Pseudoxanthoma Elasticum.Journal of clinical medicine · 2021Article
- Tissue-Nonspecific Alkaline Phosphatase-A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease.Biomolecules · 2020Review
- Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling Pathways.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Arterial media calcification is frequently seen in elderly and patients with chronic kidney disease (CKD), diabetes and osteoporosis. Pyrophosphate is a well-known calcification inhibitor that binds to nascent hydroxyapatite crystals and prevents further incorporation of inorganic phosphate into these crystals. However, the enzyme tissue-nonspecific alkaline phosphatase (TNAP), which is expressed in calcified arteries, degrades extracellular pyrophosphate into phosphate ions, by which pyrophosphate loses its ability to block vascular calcification. Here, we aimed to evaluate whether pharmacological TNAP inhibition is able to prevent the development of arterial calcification in a rat model of warfarin-induced vascular calcification. To investigate the effect of the pharmacological TNAP inhibitor SBI-425 on vascular calcification and bone metabolism, a 0.30% warfarin rat model was used. Warfarin exposure resulted in distinct calcification in the aorta and peripheral arteries. Daily administration of the TNAP inhibitor SBI-425 (10 mg/kg/day) for 7 weeks significantly reduced vascular calcification as indicated by a significant decrease in calcium content in the aorta (vehicle 3.84 ± 0.64 mg calcium/g wet tissue vs TNAP inhibitor 0.70 ± 0.23 mg calcium/g wet tissue) and peripheral arteries and a distinct reduction in area % calcification on Von Kossa stained aortic sections as compared to vehicle. Administration of SBI-425 resulted in decreased bone formation rate and mineral apposition rate, and increased osteoid maturation time and this without significant changes in osteoclast- and eroded perimeter. Administration of TNAP inhibitor SBI-425 significantly reduced the calcification in the aorta and peripheral arteries of a rat model of warfarin-induced vascular calcification. However, suppression of TNAP activity should be limited in order to maintain adequate physiological bone mineralization.
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.