ArticlePloS one2017
Extracellular calcium promotes bone formation from bone marrow mesenchymal stem cells by amplifying the effects of BMP-2 on SMAD signalling.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 89 citations in OpenAlex.
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- Dextromethorphan Modulates the Osteogenic-Adipogenic Balance in Rat Bone Marrow Mesenchymal Stem Cells.Cells · 2026Article
- Mcu regulates bone formation via mitochondrial calcium uptake and lineage allocation.Experimental & molecular medicine · 2026Article
- P2X7 is an important mediator of BMP9-induced osteogenic differentiation of mesenchymal stem cells.Cell communication and signaling : CCS · 2026Article
- Targeted drug repurposing in medication-related osteonecrosis of the jaw: a review of teriparatide and pentoxifylline/α-tocopherol protocols.Frontiers in medicine · 2026Review
- Efficient differentiation of gonadal somatic cell-like cells (GSCLCs) using magnetic nanoparticles from mouse embryonic stem cells.American journal of translational research · 2026Article
- Dose-dependent osteoimmunomodulatory effects of amorphous calcium phosphate nanoparticles promote 3D-printed scaffold-mediated bone regeneration.Bioactive materials · 2025Article
- Synthesis and Osteoinductive Properties of Nanosized Lithium-Modified Calcium-Organic Frameworks.Materials (Basel, Switzerland) · 2025Article
- miR-125b differentially impacts mineralization in dexamethasone and calcium-treated human mesenchymal stem cells.Molecular therapy. Nucleic acids · 2025Article
- Evaluating Bioassays for the Determination of Simvastatin's Osteogenic Activity: A Systematic Review.Journal of functional biomaterials · 2025Review
- Exploring Metabolic Mechanisms in Calcific Tendinopathy and Shoulder Arthrofibrosis: Insights and Therapeutic Implications.Journal of clinical medicine · 2024Review
- Molecular mechanism of BMP signal control by Twisted gastrulation.Nature communications · 2024Article
- Article
- Bioactive Porous Composite Implant Guides Mesenchymal Stem Cell Differentiation and Migration to Accelerate Bone Reconstruction.International journal of nanomedicine · 2024Article
- Osteo-inductive effect of piezoelectric stimulation from the poly(l-lactic acid) scaffolds.PloS one · 2024Article
- Research Progress on the Osteogenesis-Related Regulatory Mechanisms of Human Umbilical Cord Mesenchymal Stem Cells.Stem cell reviews and reports · 2023Review
- Article
- Ginsenosides on stem cells fate specification-a novel perspective.Frontiers in cell and developmental biology · 2023Review
- Characterization of eggshell as a bio-regeneration material.Medicine and pharmacy reports · 2023Article
- Mimicking Bone Extracellular Matrix: From BMP-2-Derived Sequences to Osteogenic-Multifunctional Coatings.Advanced healthcare materials · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the molecular events that regulate osteoblast differentiation is essential for the development of effective approaches to bone regeneration. In this study, we analysed the osteoinductive properties of extracellular calcium in bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation. We cultured BM-MSCs in 3D gelatin scaffolds with Ca2+ and BMP-2 as osteoinductive agents. Early and late osteogenic gene expression and bone regeneration in a calvarial critical-size defect model demonstrate that extracellular Ca2+ enhances the effects of BMP-2 on Osteocalcin, Runx2 and Osterix expression and promotes bone regeneration in vivo. Moreover, we analysed the molecular mechanisms involved and observed an antagonistic effect between Ca2+ and BMP-2 on SMAD1/5, ERK and S6K signalling after 24 hours. More importantly, a cooperative effect between Ca2+ and BMP-2 on the phosphorylation of SMAD1/5, S6, GSK3 and total levels of β-CATENIN was observed at a later differentiation time (10 days). Furthermore, Ca2+ alone favoured the phosphorylation of SMAD1, which correlates with the induction of Bmp2 and Bmp4 gene expression. These data suggest that Ca2+ and BMP-2 cooperate and promote an autocrine/paracrine osteogenic feed-forward loop. On the whole, these results demonstrate the usefulness of calcium-based bone grafts or the addition of exogenous Ca2+ in bone tissue engineering.
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