ArticleKidney international2011
Hyperphosphatemia-induced nanocrystals upregulate the expression of bone morphogenetic protein-2 and osteopontin genes in mouse smooth muscle cells in vitro.
Article in Kidney international, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
What it found
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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
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.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 210 citations in OpenAlex.
- Pooled it
- The effect of lanthanum carbonate on calciprotein particles in hemodialysis patients.Clinical and experimental nephrology · 2020Trial
- Control of metabolic predisposition to cardiovascular complications of chronic kidney disease by effervescent calcium magnesium citrate: a feasibility study.Journal of nephrology · 2019Trial
- Review
- Factors associated with vascular calcification in peritoneal dialysis patients: a meta-analysis.International urology and nephrology · 2026Article
- Senescent cells in systemic aging: SASP heterogeneity, immune escape, and endocrine modulation.Biogerontology · 2026Review
- Comprehensive Review of Mechanisms and Translational Perspectives on Programmed Cell Death in Vascular Calcification.Biomolecules · 2025Review
- Bioinspired Collagen/κ-Carrageenan 3D Matrix forACS biomaterials science & engineering · 2025Article
- Elevated phosphate levels in CKD - a direct threat for the heart.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Mechanism of influence of calcified nanoparticles in the development of calcified diseases (Review).Biomedical reports · 2025Review
- Relationship of serum phosphorus level with acute cerebrovascular disease.Scientific reports · 2025Article
- Pathophysiology and therapies of CKD-associated secondary hyperparathyroidism.Clinical kidney journal · 2025Article
- Exploring Bone Morphogenetic Protein-2 and -4 mRNA Expression and Their Receptor Assessment in a DynamicCells · 2024Article
- A Meta-Analysis on Quantitative Calcium, Phosphorus and Magnesium Metabolism in Horses and Ponies.Animals : an open access journal from MDPI · 2024Review
- Inorganic Pyrophosphate at Serum Concentration May Not Be Able to Inhibit Mineralization: A Study in Aqueous Solutions and Serum.ACS omega · 2024Article
- Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles.Bone research · 2024Article
- Review
- Key regulators of vascular calcification in chronic kidney disease: Hyperphosphatemia, BMP2, and RUNX2.PeerJ · 2024Review
- Higher serum phosphate within the normal range is associated with the development of calcified aortic valve disease.Frontiers in cardiovascular medicine · 2024Article
- Similarities and Differences of Vascular Calcification in Diabetes and Chronic Kidney Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
52 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Vascular calcification, which contributes to cardiovascular disease in patients with uremic hyperphosphatemia, is associated with vascular cell expression of osteogenic genes, including bone morphogenetic protein (BMP)-2 and osteopontin (OPN). High inorganic phosphate levels in vitro stimulate the osteogenic conversion of smooth muscle cells; however, the mechanism governing this is not clear. We found that high-phosphate medium increased the expression of BMP-2 and OPN in mouse smooth muscle cells in culture. However, this effect was lost in the presence of the mineralization inhibitor, pyrophosphate, suggesting a contribution of calcium phosphate crystals. Addition of 1-2 mmol/l phosphate alone to growth medium was sufficient to induce nanosized crystals after 1 day at 37 °C. Isolated crystals were about 160 nm in diameter and had a calcium to phosphate ratio of 1.35, consistent with the hydroxyapatite precursor octacalcium phosphate. Nanocrystal formation increased fourfold in the absence of serum, was blocked by fetuin-A, and was dependent on time and on the concentrations of phosphate and calcium. Purified synthetic hydroxyapatite nanocrystals and isolated high-phosphate-induced nanocrystals, but not nanocrystal-free high-phosphate medium, also induced BMP-2 and OPN. Thus, our results suggest that BMP-2 and OPN are induced by calcium phosphate nanocrystals, rather than soluble phosphate. This mechanism may contribute, in part, to hyperphosphatemia-related vascular cell differentiation and calcification.
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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.