ArticleFrontiers in endocrinology2012
The P2X7 Receptor is an Important Regulator of Extracellular ATP Levels.
Article in Frontiers in endocrinology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 135 citations in OpenAlex.
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- P2X7R Signaling and Differential Regulation of Neuroinflammatory and Behavior Responses in Male and Female Mice During Chronic Ethanol Exposure.International journal of molecular sciences · 2026Article
- Article
- Neuroinflammatory responses and blood-brain barrier injury in chronic alcohol exposure: role of purinergic P2 × 7 Receptor signaling.Journal of neuroinflammation · 2024Article
- "Find Me" and "Eat Me" signals: tools to drive phagocytic processes for modulating antitumor immunity.Cancer communications (London, England) · 2024Review
- Mechanical stimulation-induced purinome priming fosters osteogenic differentiation and osteointegration of mesenchymal stem cells from the bone marrow of post-menopausal women.Stem cell research & therapy · 2024Article
- Pathological calcification in canine tendon-derived cells is modulated by extracellular ATP.Veterinary research communications · 2024Article
- Neuroinflammatory Responses and Blood-Brain Barrier Injury in Chronic Alcohol Exposure: Role of Purinergic P2X7 Receptor Signaling.Research square · 2024Article
- Modulation of osteoblast differentiation and function by the P2X4 receptor.Purinergic signalling · 2023Article
- Silencing NTPDase3 activity rehabilitates the osteogenic commitment of post-menopausal stem cell bone progenitors.Stem cell research & therapy · 2023Article
- P2X7Rs: new therapeutic targets for osteoporosis.Purinergic signalling · 2023Review
- The circadian regulation of extracellular ATP.Purinergic signalling · 2023Review
- P2RX7 promotes osteosarcoma progression and glucose metabolism by enhancing c-Myc stabilization.Journal of translational medicine · 2023Article
- Extracellular ATP and its derivatives provide spatiotemporal guidance for bone adaptation to wide spectrum of physical forces.Bone reports · 2022Review
- Mechanical Disturbance of Osteoclasts Induces ATP Release That Leads to Protein Synthesis in Skeletal Muscle through an Akt-mTOR Signaling Pathway.International journal of molecular sciences · 2022Article
- A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling.Purinergic signalling · 2022Review
- The Multifaceted Actions of CD73 During Development and Suppressive Actions of Regulatory T Cells.Frontiers in immunology · 2022Review
- Augmentation of Extracellular ATP Synergizes With Chemotherapy in Triple Negative Breast Cancer.Frontiers in oncology · 2022Article
- Protective Effect of Purinergic P2X7 Receptor Inhibition on Acrolein-Induced Urothelial Cell Damage.Frontiers in physiology · 2022Article
- Restraint of Human Skin Fibroblast Motility, Migration, and Cell Surface Actin Dynamics, by Pannexin 1 and P2X7 Receptor Signaling.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Controlled ATP release has been demonstrated from many neuronal and non-neuronal cell types. Once released, extracellular ATP acts on cells in a paracrine manner via purinergic receptors. Considerable evidence now suggests that extracellular nucleotides, signaling via P2 receptors, play important roles in bone homeostasis modulating both osteoblast and osteoclast function. In this study, we demonstrate that mouse osteoclasts and their precursors constitutively release ATP into their extracellular environment. Levels were highest at day 2 (precursor cells), possibly reflecting the high number of red blood cells and accessory cells present. Mature osteoclasts constitutively released ATP in the range 0.05-0.5 pmol/ml/cell. Both osteoclasts and osteoblasts express mRNA and protein for the P2X7 receptor. We found that in osteoclasts, expression levels are fourfold higher in mature cells relative to precursors, whilst in osteoblasts expression remains relatively constant during differentiation. Selective antagonists (0.1-100 μM AZ10606120, A438079, and KN-62) were used to determine whether this release was mediated via P2X7 receptors. AZ10606120, A438079, and KN-62, at 0.1-10 μM, decreased ATP release by mature osteoclasts by up to 70, 60, and 80%, respectively. No differences in cell viability were observed. ATP release also occurs via vesicular exocytosis; inhibitors of this process (1-100 μM NEM or brefeldin A) had no effect on ATP release from osteoclasts. P2X7 receptor antagonists (0.1-10 μM) also decreased ATP release from primary rat osteoblasts by up to 80%. These data show that ATP release via the P2X7 receptor contributes to extracellular ATP levels in osteoclast and osteoblast cultures, suggesting an important additional role for this receptor in autocrine/paracrine purinergic signaling in bone.
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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.