ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
Direct or indirect stimulation of adenosine A2A receptors enhances bone regeneration as well as bone morphogenetic protein-2.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Involvement of adenosine signaling pathway in migraine pathophysiology: a systematic review of preclinical studies.The journal of headache and pain · 2022Pooled it
- Dipyridamole-Coated 3D-Printed β-Tricalcium Phosphate Scaffolds: Spectrophotometric Characterization, Drug Release Kinetics, and In Vitro Evaluation to Guide Critical-Sized Bone Defect Repair Studies.Journal of functional biomaterials · 2026Article
- Reply.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Phosphodiesterase inhibitors as emerging therapeutics for skeletal disorders: A comprehensive review of mechanisms and repurposing potential.Bone reports · 2026Review
- Polydeoxyribonucleotide (PDRN) Selectively Promotes Osteoblast Differentiation Without Affecting Osteoclastogenesis.Marine drugs · 2026Article
- Cranial Defect Reconstruction With Custom 3D-Printed Hydroxyapatite Scaffolds Augmented With rhBMP-2 or Dipyridamole in a Nonhuman Primate Model.Journal of tissue engineering and regenerative medicine · 2026Article
- Modern Approaches and Emerging Biological Therapies to Treat Fracture Nonunion.Pharmaceutics · 2025Review
- Enabling adenosine signaling to promote aged fracture healing.NPJ Regenerative medicine · 2025Article
- Adenosine metabolism and receptors in aging of the skin, musculoskeletal, immune and cardiovascular systems.Ageing research reviews · 2025Review
- Combination treatment with anti-RANKL and antibiotics for preventing joint destruction in septic arthritis.JCI insight · 2025Article
- The function of GPCRs in different bone cells.International journal of biological sciences · 2025Review
- Versatile and Marvelous Potentials of Polydeoxyribonucleotide for Tissue Engineering and Regeneration.Biomaterials research · 2025Review
- Augmentation of Deficient Bone Healing by Pulsed Electromagnetic Fields-From Mechanisms to Clinical Outcomes.Bioengineering (Basel, Switzerland) · 2024Review
- Biomimetic Tissue Engineering Strategies for Craniofacial Applications.Biomimetics (Basel, Switzerland) · 2024Review
- Functional Scaffolds for Bone Tissue Regeneration: A Comprehensive Review of Materials, Methods, and Future Directions.Journal of functional biomaterials · 2024Review
- Translational Experimental Basis of Indirect Adenosine Receptor Agonist Stimulation for Bone Regeneration: A Review.International journal of molecular sciences · 2024Review
- Ticagrelor was associated with lower fracture risk than clopidogrel in the dual anti-platelet regimen among patients with acute coronary syndrome treated with percutaneous coronary intervention.Journal of endocrinological investigation · 2024Article
- Three-Dimensional Printing Methods for Bioceramic-Based Scaffold Fabrication for Craniomaxillofacial Bone Tissue Engineering.Journal of functional biomaterials · 2024Review
- Multi-Functional Small Molecule Alleviates Fracture Pain and Promotes Bone Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Bone Tissue Engineering (BTE) of the Craniofacial Skeleton, Part I: Evolution and Optimization of 3D-Printed Scaffolds for Repair of Defects.The Journal of craniofacial surgery · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Promoting bone regeneration and repair of bone defects is a need that has not been well met to date. We have previously found that adenosine, acting via A2A receptors (A2AR) promotes wound healing and inhibits inflammatory osteolysis and hypothesized that A2AR might be a novel target to promote bone regeneration. Therefore, we determined whether direct A2AR stimulation or increasing endogenous adenosine concentrations via purine transport blockade with dipyridamole regulates bone formation. We determined whether coverage of a 3 mm trephine defect in a mouse skull with a collagen scaffold soaked in saline, bone morphogenetic protein-2 (BMP-2; 200 ng), 1 μM CGS21680 (A2AR agonist, EC50 = 160 nM), or 1 μM dipyridamole (EC50 = 32 nM) promoted bone regeneration. Microcomputed tomography examination demonstrated that CGS21680 and dipyridamole markedly enhanced bone regeneration as well as BMP-2 8 wk after surgery (60 ± 2%, 79 ± 2%, and 75 ± 1% bone regeneration, respectively, vs. 32 ± 2% in control, P < 0.001). Blockade by a selective A2AR antagonist (ZM241385, 1 μM) or deletion of A2AR abrogated the effect of CGS21680 and dipyridamole on bone regeneration. Both CGS21680 and dipyridamole treatment increased alkaline phosphatase-positive osteoblasts and diminished tartrate resistance acid phosphatase-positive osteoclasts in the defects. In vivo imaging with a fluorescent dye for new bone formation revealed a strong fluorescent signal in treated animals that was equivalent to BMP-2. In conclusion, stimulation of A2AR by specific agonists or by increasing endogenous adenosine levels stimulates new bone formation as well as BMP-2 and represents a novel approach to stimulating bone regeneration.
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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.