The DOI matches its Crossref record; 53 of the 54 references it cites were found in a registry or an index.
Direct or indirect stimulation of adenosine A 2A receptors enhances bone regeneration as well as bone morphogenetic protein‐2
Open accessAbstract
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 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, EC 50 = 160 nM), or 1 μM dipyridamole (EC 50 = 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.—Mediero, A., Wilder, T., Perez‐Aso, M., Cronstein, B. N. Direct or indirect stimulation of adenosine A 2A receptors enhances bone regeneration as well as bone morphogenetic protein‐2. FASEB J. 29, 1577‐1590 (2015). www.fasebj.org
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Evidence has shown that a major mechanism of caffeine in organs is its direct and indirect effects on bone metabolism through competitive inhibition of four adenosine receptors, including A1, A2A, A2B and A3 adenosine, which are expressed in undifferentiated osteoblast precursors and differentiated osteoblasts [41, 42].”
From Association between caffeine consumption and bone mineral density in children and adolescent: Observational and Mendelian randomization study (2023) · cites this paper as [42]
Citations
Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610
Carragee, E. J., Hurwitz, E. L., & Weiner, B. K. (2011) · The Spine Journal · doi:10.1016/j.spinee.2011.04.023 · Cited by 1,393
The Critical Size Defect as an Experimental Model for Craniomandibulofacial Nonunions
Schmitz, J. P., & Hollinger, J. O. (1986) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-198604000-00036 · Cited by 1,324
Fredholm, B. B., IJzerman, A. P., Jacobson, K. A., Linden, J. M., & Müller, C. E. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.003285 · Cited by 1,307
Bone remodeling during fracture repair: The cellular picture
Schindeler, A., McDonald, M. M., Bokko, P. B., & Little, D. G. (2008) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2008.07.004 · Cited by 986
Boden, S. D., Kang, J. D., Sandhu, H. S., & Heller, J. G. (2002) · Spine · doi:10.1097/00007632-200212010-00005 · Cited by 694
Methotrexate—how does it really work?
Chan, E. S. L., & Cronstein, B. N. (2010) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.5 · Cited by 464
Self-citationMolecular aspects of fracture healing:Which are the important molecules?
Tsiridis, E. E., Upadhyay, N., & Giannoudis, P. V. (2007) · Injury · doi:10.1016/j.injury.2007.02.006 · Cited by 366
HIF-1–dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia
Eltzschig, H. K., ABDULLA, P. R., Hoffman, E., Hamilton, K. E., Daniels, D., Schönfeld, C., Löffler, M., Reyes, G., Duszenko, M., Karhausen, J., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050177 · Cited by 352
Riley, E. H., Lane, J. M., Urist, M. R., Lyons, K. M., & Lieberman, J. R. (1996) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-199603000-00006 · Cited by 309
Flagged first, then by citations
1 of the 54 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 101–103 of 103
Marco-Bonilla, M., Mediero, A., & Fresnadillo, M. J. (2026) · Arthritis & Rheumatology · doi:10.1002/art.70171
Self-citationLee, C., Tseng, K., Lin, F., Wu, H., & Lin, S. (2026) · BioFactors · doi:10.1002/biof.70140
Rasane, P., Nayak, V. V., Arachchige, L. C. W., Rice, E., Ashin, Z. F., Venkatesan, B., Varanasi, V. G., Ono, N., Young, S. W., & Witek, L. (2026) · Journal of Functional Biomaterials · doi:10.3390/jfb17080396
Metadata
- Authors
- Mediero, A., Wilder, T., Perez‐Aso, M., & Cronstein, B. N.
- Affiliations
- NYU Langone Health (US)
- Divisions of Translational Medicine and Rheumatology Department of Medicine New York University Langone Medical Center New York New York USA
- Corresponding author
- Cronstein, Bruce N.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2015-01-08
- Volume
- 29
- Issue
- 4
- Pages
- 1577-1590
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- PMC
- PMC4396602
- OpenAlex
- W2124167914
- Cited by
- 103
- References
- 54
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 8 · 2023: 11 · 2022: 13 · 2021: 8 · 2020: 8 · 2019: 12 · 2018: 12 · 2017: 7 · 2016: 7 · 2015: 2
- FWCI
- 7.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The FASEB Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AR56672, AR54897, AR046121)
- Takeda Pharmaceuticals North America
- Celgene
- AstraZeneca
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- adenosine A2A receptor, bone regeneration, BMP-2, dipyridamole, CGS 21680, ZM241385, osteoblasts, osteoclasts, calvarial defect, endogenous adenosine, bone formation
- MeSH terms
- Adenosine, Animals, Bone Regeneration, Cell Count, Dipyridamole, Female, Mice, Inbred C57BL, Osteoblasts, Osteoclasts, Phenethylamines, Mice, Knockout, Receptor, Adenosine A2A, Mice, Bone Morphogenetic Protein 2, Adenosine A2 Receptor Agonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
