ArticleProceedings of the National Academy of Sciences of the United States of America2004
Physiological changes in extracellular calcium concentration directly control osteoblast function in the absence of calciotropic hormones.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
119 citing papers in PubMed, 1 synthesis or guideline pooled it, 435 citations in OpenAlex.
- Mechanisms and traditional Chinese medicine therapeutics for primary osteoporosis: an integrated perspective.Frontiers in endocrinology · 2025Pooled it
- Bone Matrix Mineralization in Patients With Gain-of-Function Calcium-Sensing Receptor Mutations Is Distinctly Different From that in Postsurgical Hypoparathyroidism.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Trial
- Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism.Clinical journal of the American Society of Nephrology : CJASN · 2015Trial
- Cinacalcet lowers serum alkaline phosphatase in maintenance hemodialysis patients.Clinical journal of the American Society of Nephrology : CJASN · 2009Trial
- Article
- Effect of Octacalcium Phosphate on Osteogenic Differentiation of Induced Pluripotent Stem Cells in a 3D Hybrid Spheroid Culture.Biomimetics (Basel, Switzerland) · 2025Article
- The role of calcium ions and the transient receptor potential vanilloid (TRPV) channel in bone remodelling and orthodontic tooth movement.Molecular biology reports · 2025Review
- Multifunctional Bionic Periosteum with Ion Sustained-Release for Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Bone targeted nano-drug and nano-delivery.Bone research · 2024Review
- Calcium-based phosphate binders and bone mineral density in patients undergoing hemodialysis: a retrospective cohort study.Clinical and experimental nephrology · 2024Article
- Article
- Exploring the relationship between calcitonin, ionized calcium, and bone turnover in cats with and without naturally occurring hypercalcemia.Frontiers in veterinary science · 2024Article
- Magnesium (Mg2 +), Strontium (Sr2 +), and Zinc (Zn2 +) Co-substituted Bone Cements Based on Nano-hydroxyapatite/Monetite for Bone Regeneration.Biological trace element research · 2023Article
- Rescue of High Glucose Impairment of Cultured Human Osteoblasts Using Cinacalcet and Parathyroid Hormone.Calcified tissue international · 2023Article
- The Localized Ionic Microenvironment in Bone Modelling/Remodelling: A Potential Guide for the Design of Biomaterials for Bone Tissue Engineering.Journal of functional biomaterials · 2023Review
- Optimization of the Alizarin Red S Assay by Enhancing Mineralization of Osteoblasts.International journal of molecular sciences · 2022Article
- Calcium‑dependent activation of PHEX, MEPE and DMP1 in osteocytes.Molecular medicine reports · 2022Article
- Synergistic Effect of Carbonate Apatite and Autogenous Bone on Osteogenesis.Materials (Basel, Switzerland) · 2022Article
- Calcium Phosphate-Based Biomaterials for Bone Repair.Journal of functional biomaterials · 2022Review
- Does Biphasic Calcium Phosphate-Coated Surface Increase the Secondary Stability in Dental Implants? A Split-Mouth Study.Journal of maxillofacial and oral surgery · 2022Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We investigated the direct effects of changes in free ionized extracellular calcium concentrations ([Ca2+]o) on osteoblast function and the involvement of the calcium-sensing receptor (CaR) in mediating these responses. CaR mRNA and protein were detected in osteoblast models, freshly isolated fetal rat calvarial cells and murine clonal osteoblastic 2T3 cells, and in freshly frozen, undecalcified preparations of human mandible and rat femur. In fetal rat calvarial cells, elevating [Ca2+]o and treatment with gadolinium, a nonpermeant CaR agonist, resulted in phosphorylation of the extracellular signal-regulated kinases 1 and 2, Akt, and glycogensynthase kinase 3beta, consistent with signals of cell survival and proliferation. In agreement, cell number was increased under these conditions. Expression of the osteoblast differentiation markers core binding factor alpha1, osteocalcin, osteopontin, and collagen I mRNAs was increased by high [Ca2+]o, as was mineralized nodule formation. Alkaline phosphatase activity was maximal for [Ca2+]o between 1.2 and 1.8 mM. Inhibition of CaR by NPS 89636 blocked responses to the CaR agonists. In conclusion, we show that small deviations of [Ca2+]o from physiological values have a profound impact on bone cell fate, by means of the CaR and independently of systemic calciotropic peptides.
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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.