ArticleJournal of cellular physiology2013
An integrated understanding of the physiological response to elevated extracellular phosphate.
Article in Journal of cellular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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
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Who cites it
54 citing papers in PubMed, 109 citations in OpenAlex.
- Toward improved phosphorus efficiency in monogastrics-interplay of serum, minerals, bone, and immune system after divergent dietary phosphorus supply in swine.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Trial
- Impact of Phosphorus-Based Food Additives on Bone and Mineral Metabolism.The Journal of clinical endocrinology and metabolism · 2015Trial
- Zinc-Containing Bioactive Glass Programs Macrophage Polarization through Extracellular Traps Regulation for Enhanced Diabetic Wound Healing.Advanced healthcare materials · 2026Article
- TGFβ signaling regulates the response of the skeleton to phosphate.bioRxiv : the preprint server for biology · 2025Article
- Osteoblasts sense extracellular levels of phosphate to control the local expression of phosphatases for matrix mineralisation.Bone reports · 2025Article
- Organic phosphate but not inorganic phosphate regulatesiScience · 2024Article
- The Intricacies of Renal Phosphate Reabsorption-An Overview.International journal of molecular sciences · 2024Review
- Cranial Neural Crest Specific Deletion ofInternational journal of molecular sciences · 2023Article
- Sclerostin small-molecule inhibitors promote osteogenesis by activating canonical Wnt and BMP pathways.eLife · 2023Article
- Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice.JCI insight · 2023Article
- Mild Chronic Kidney Disease Associated with Low Bone Formation and Decrease in Phosphate Transporters and Signaling Pathways Gene Expression.International journal of molecular sciences · 2023Article
- β-TCP from 3D-printed composite scaffolds acts as an effective phosphate source during osteogenic differentiation of human mesenchymal stromal cells.Frontiers in cell and developmental biology · 2023Article
- Influence of Biomimetically Mineralized Collagen Scaffolds on Bone Cell Proliferation and Immune Activation.Polymers · 2022Article
- Phosphate Toxicity and Epithelial to Mesenchymal Transition.Advances in experimental medicine and biology · 2022Article
- Extracellular Phosphate, Inflammation and Cytotoxicity.Advances in experimental medicine and biology · 2022Review
- Pathophysiology of Vascular Calcification and Bone Loss: Linked Disorders of Ageing?Nutrients · 2021Review
- Silicon Oxynitrophosphide Nanoscale Coating Enhances Antioxidant Marker-Induced Angiogenesis During in vivo Cranial Bone-Defect Healing.JBMR plus · 2021Article
- Modulating phosphate consumption, a novel therapeutic approach for the control of cancer cell proliferation and tumorigenesis.Biochemical pharmacology · 2021Review
- Phosphate as a Signaling Molecule.Calcified tissue international · 2021Review
- Excessive Inorganic Phosphate Burden Perturbed Intracellular Signaling: Quantitative Proteomics and Phosphoproteomics Analyses.Frontiers in nutrition · 2021Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
Recent studies have suggested that changes in serum phosphate levels influence pathological states associated with aging such as cancer, bone metabolism, and cardiovascular function, even in individuals with normal renal function. The causes are only beginning to be elucidated but are likely a combination of endocrine, paracrine, autocrine, and cell autonomous effects. We have used an integrated quantitative biology approach, combining transcriptomics and proteomics to define a multi-phase, extracellular phosphate-induced, signaling network in pre-osteoblasts as well as primary human and mouse mesenchymal stromal cells. We identified a rapid mitogenic response stimulated by elevated phosphate that results in the induction of immediate early genes including c-fos. The mechanism of activation requires FGF receptor signaling followed by stimulation of N-Ras and activation of AP-1 and serum response elements. A distinct long-term response also requires FGF receptor signaling and results in N-Ras activation and expression of genes and secretion of proteins involved in matrix regulation, calcification, and angiogenesis. The late response is synergistically enhanced by addition of FGF23 peptide. The intermediate phase results in increased oxidative phosphorylation and ATP production and is necessary for the late response providing a functional link between the phases. Collectively, the results define elevated phosphate, as a mitogen and define specific mechanisms by which phosphate stimulates proliferation and matrix regulation. Our approach provides a comprehensive understanding of the cellular response to elevated extracellular phosphate, functionally connecting temporally coordinated signaling, transcriptional, and metabolic events with changes in long-term cell behavior.
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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.