ArticleStem cells and development2013
Extracellular purines promote the differentiation of human bone marrow-derived mesenchymal stem cells to the osteogenic and adipogenic lineages.
Article in Stem cells and development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 109 citations in OpenAlex.
- MSTNCells · 2026Article
- G protein-coupled receptor signaling in osteogenic bone mesenchymal stem/stromal cells.Frontiers in cell and developmental biology · 2026Review
- Enhancing retention and quality of tissue stromal vascular fraction graft with globo H ceramide.Stem cell research & therapy · 2025Article
- Metabolic markers detect early ostedifferentiation of mesenchymal stem cells from multiple donors.Stem cell research & therapy · 2025Article
- Mechanosignaling in Osteoporosis: When Cells Feel the Force.International journal of molecular sciences · 2025Review
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Role of Neurotransmitters in Steady State Hematopoiesis, Aging, and Leukemia.Stem cell reviews and reports · 2025Review
- Effects of ATP on the Physicochemical Properties and Cytocompatibility of Calcium Sulfate/Calcium Citrate Composite Cement.Materials (Basel, Switzerland) · 2023Article
- Purinergic receptor: a crucial regulator of adipose tissue functions.Purinergic signalling · 2023Review
- The ATP-dependent Pathways and Human Diseases.Current medicinal chemistry · 2023Article
- CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche.International journal of molecular sciences · 2022Article
- NMR Metabolomics Assessment of Osteogenic Differentiation of Adipose-Tissue-Derived Mesenchymal Stem Cells.Journal of proteome research · 2022Article
- Connexins in the development and physiology of stem cells.Tissue barriers · 2021Review
- Purinergic signaling in diabetes and metabolism.Biochemical pharmacology · 2021Review
- In Search of a Role for Extracellular Purine Enzymes in Bone Function.Biomolecules · 2021Review
- Article
- Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling Pathways.International journal of molecular sciences · 2020Review
- Sustained Release of Magnesium Ions Mediated by a Dynamic Mechanical Hydrogel to Enhance BMSC Proliferation and Differentiation.ACS omega · 2020Article
- Adult mesenchymal stem cells: is there a role for purine receptors in their osteogenic differentiation?Purinergic signalling · 2020Review
- Immortalization of Mesenchymal Stromal Cells by TERT Affects Adenosine Metabolism and Impairs their Immunosuppressive Capacity.Stem cell reviews and reports · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular nucleotides are potent signaling molecules mediating cell-specific biological functions, mostly within the processes of tissue damage and repair and flogosis. We previously demonstrated that adenosine 5'-triphosphate (ATP) inhibits the proliferation of human bone marrow-derived mesenchymal stem cells (BM-hMSCs), while stimulating, in vitro and in vivo, their migration. Here, we investigated the effects of ATP on BM-hMSC differentiation capacity. Molecular analysis showed that ATP treatment modulated the expression of several genes governing adipogenic and osteoblastic (i.e., WNT-pathway-related genes) differentiation of MSCs. Functional studies demonstrated that ATP, under specific culture conditions, stimulated adipogenesis by significantly increasing the lipid accumulation and the expression levels of the adipogenic master gene PPARγ (peroxisome proliferator-activated receptor-gamma). In addition, ATP stimulated osteogenic differentiation by promoting mineralization and expression of the osteoblast-related gene RUNX2 (runt-related transcription factor 2). Furthermore, we demonstrated that ATP stimulated adipogenesis via its triphosphate form, while osteogenic differentiation was induced by the nucleoside adenosine, resulting from ATP degradation induced by CD39 and CD73 ectonucleotidases expressed on the MSC membrane. The pharmacological profile of P2 purinergic receptors (P2Rs) suggests that adipogenic differentiation is mainly mediated by the engagement of P2Y1 and P2Y4 receptors, while stimulation of the P1R adenosine-specific subtype A2B is involved in adenosine-induced osteogenic differentiation. Thus, we provide new insights into molecular regulation of MSC differentiation.
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