ArticleInternational journal of molecular medicine2016
Regulation of the osteogenic and adipogenic differentiation of bone marrow-derived stromal cells by extracellular uridine triphosphate: The role of P2Y2 receptor and ERK1/2 signaling.
Article in International journal of molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Knowledge domain and evolutionary trends of P2Y receptors in cardiovascular diseases: a bibliometric and altmetric analysis.Frontiers in pharmacology · 2025Pooled it
- MiR-210 promotes bone formation in ovariectomized rats by regulating osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells through downregulation of EPHA2.Journal of orthopaedic surgery and research · 2023Article
- Modulation of osteoblast differentiation and function by the P2X4 receptor.Purinergic signalling · 2023Article
- Therapeutic potential for P2YPurinergic signalling · 2023Review
- CaInternational journal of molecular sciences · 2023Review
- Purinergic receptor: a crucial regulator of adipose tissue functions.Purinergic signalling · 2023Review
- ATP-induced cell death: a novel hypothesis for osteoporosis.Frontiers in cell and developmental biology · 2023Review
- Adipocyte purinergic receptors activated by uracil nucleotides as obesity and type 2 diabetes targets.Current opinion in pharmacology · 2022Review
- miRNA-Gene Interaction Network Construction Strategy to Discern Promising Traditional Chinese Medicine against Osteoporosis.BioMed research international · 2022Article
- Purinergic signaling in diabetes and metabolism.Biochemical pharmacology · 2021Review
- Exosomal miR-335 derived from mature dendritic cells enhanced mesenchymal stem cell-mediated bone regeneration of bone defects in athymic rats.Molecular medicine (Cambridge, Mass.) · 2021Article
- P2Y Receptors in Bone - Anabolic, Catabolic, or Both?Frontiers in endocrinology · 2021Review
- The P2X7 ion channel is dispensable for energy and metabolic homeostasis of white and brown adipose tissues.Purinergic signalling · 2020Article
- Effect of autophagy on irradiation‑induced damage in osteoblast‑like MC3T3‑E1 cells.Molecular medicine reports · 2020Article
- Adult mesenchymal stem cells: is there a role for purine receptors in their osteogenic differentiation?Purinergic signalling · 2020Review
- Identification and characterization of adipose surface epitopes.The Biochemical journal · 2020Review
- P2YFrontiers in endocrinology · 2020Article
- P2X7 Receptor in the Management of Energy Homeostasis: Implications for Obesity, Dyslipidemia, and Insulin Resistance.Frontiers in endocrinology · 2020Review
- Exosomes derived from human umbilical cord blood mesenchymal stem cells improve hepatic ischemia reperfusion injury via delivering miR-1246.Cell cycle (Georgetown, Tex.) · 2019Article
- Mechanical strain triggers differentiation of dental mesenchymal stem cells by activating osteogenesis-specific biomarkers expression.American journal of translational research · 2019Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An imbalance in the osteogenesis and adipogenesis of bone marrow-derived stromal cells (BMSCs) is a crucial pathological factor in the development of osteoporosis. Growing evidence suggests that extracellular nucleotide signaling involving the P2 receptors plays a significant role in bone metabolism. The aim of the present study was to investigate the effects of uridine triphosphate (UTP) on the osteogenic and adipogenic differentiation of BMSCs, and to elucidate the underlying mechanisms. The differentiation of the BMSCs was determined by measuring the mRNA and protein expression levels of osteogenic- and adipogenic-related markers, alkaline phosphatase (ALP) staining, alizarin red staining and Oil Red O staining. The effects of UTP on BMSC differentiation were assayed using selective P2Y receptor antagonists, small interfering RNA (siRNA) and an intracellular signaling inhibitor. The incubation of the BMSCs with UTP resulted in a dose-dependent decrease in osteogenesis and an increase in adipogenesis, without affecting cell proliferation. Significantly, siRNA targeting the P2Y2 receptor prevented the effects of UTP, whereas the P2Y6 receptor antagonist (MRS2578) and siRNA targeting the P2Y4 receptor had little effect. The activation of P2Y receptors by UTP transduced to the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. This transduction was prevented by the mitogen-activated protein kinase inhibitor (U0126) and siRNA targeting the P2Y2 receptor. U0126 prevented the effects of UTP on osteogenic- and adipogenic-related gene expression after 24 h of culture, as opposed to 3 to 7 days of culture. Thus, our data suggest that UTP suppresses the osteogenic and enhances the adipogenic differentiation of BMSCs by activating the P2Y2 receptor. The ERK1/2 signaling pathway mediates the early stages of this process.
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