Evidence map›Paper›PMID 23647065›Full record

ArticleBritish journal of pharmacology2013

Activation of adenosine A(2A) receptor reduces osteoclast formation via PKA- and ERK1/2-mediated suppression of NFκB nuclear translocation.

Aránzazu Mediero, Miguel Perez-Aso, Bruce N Cronstein

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
6.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 95 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Caffeine displays dual effect on RANKL-induced osteoclast differentiation and bone resorption activity via adenosine receptors in RAW 264.7 cells.Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie · 2025
    Article
  5. Review
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  8. Energy Regulation in Inflammatory Sarcopenia by the Purinergic System.International journal of molecular sciences · 2023
    Review
  9. Review
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  13. [Effects and mechanism of morroniside on osteogenic differentiation and proliferation of mouse MC3T3-E1 cells].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2022
    Article
  14. Adenosine ABritish journal of pharmacology · 2022
    Review
  15. The effects of caffeine on bone mineral density and fracture risk.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022
    Article
  16. Article
  17. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Aránzazu MedieroDepartment of Medicine, Division of Translational Medicine, NYU School of Medicine, New York, NY 10016, USA.
Miguel Perez-Aso
Bruce N Cronstein
New York University · US

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1M
Institutional Clinical and Translational Science AwardUL1TR000038 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CRONSTEIN, BRUCE NEIL · 2012 to 2014
$16.8M
TRABECULAR BONE ADAPTATION TO MECHANICAL LOADINGP30AR046121 · NIAMS · HOSPITAL FOR SPECIAL SURGERY · PI MYERS, ELIZABETH R. · 1999 to 2010
$5.5M
The Pharmacology of Dermal Fibrosis R01AR056672 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CRONSTEIN, BRUCE NEIL · 2009 to 2018
$4.6M
Purinergic Regulation of Bone MetabolismR01AR054897 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CRONSTEIN, BRUCE NEIL · 2008 to 2014
$2.1M
The Pharmacology of Dermal FibrosisR56AR056672 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CRONSTEIN, BRUCE NEIL · 2014 to 2014
$373k
NCATS NIH HHS UL1 TR000038NCATS NIH HHS UL1TR000038NCI NIH HHS 5 P30CA16087-310NIAMS NIH HHS AR046121NIAMS NIH HHS AR54897NIAMS NIH HHS AR56672NIAMS NIH HHS AR56672S1NIAMS NIH HHS P30 AR046121NIAMS NIH HHS R01 AR054897NIAMS NIH HHS R01 AR056672NIAMS NIH HHS R56 AR056672
6 · The paper itself

Abstract

background and purposeWe previously reported that adenosine, acting at adenosine A(2A) receptors (A(2A)R), inhibits osteoclast (OC) differentiation in vitro (A(2A)R activation OC formation reduces by half) and in vivo. For a better understanding how adenosine A(2A)R stimulation regulates OC differentiation, we dissected the signalling pathways involved in A(2A)R signalling. EXPERIMENTAL APPROACH: OC differentiation was studied as TRAP+ multinucleated cells following M-CSF/RANKL stimulation of either primary murine bone marrow cells or the murine macrophage line, RAW264.7, in presence/absence of the A(2A)R agonist CGS21680, the A(2A)R antagonist ZM241385, PKA activators (8-Cl-cAMP 100 nM, 6-Bnz-cAMP) and the PKA inhibitor (PKI). cAMP was quantitated by EIA and PKA activity assays were carried out. Signalling events were studied in PKA knockdown (lentiviral shRNA for PKA) RAW264.7 cells (scrambled shRNA as control). OC marker expression was studied by RT-PCR. KEY

resultsA(2A)R stimulation increased cAMP and PKA activity which and were reversed by addition of ZM241385. The direct PKA stimuli 8-Cl-cAMP and 6-Bnz-cAMP inhibited OC maturation whereas PKI increased OC differentiation. A(2A)R stimulation inhibited p50/p105 NFκB nuclear translocation in control but not in PKA KO cells. A(2A)R stimulation activated ERK1/2 by a PKA-dependent mechanism, an effect reversed by ZM241385, but not p38 and JNK activation. A(2A)R stimulation inhibited OC expression of differentiation markers by a PKA-mechanism. CONCLUSIONS AND IMPLICATIONS: A(2A)R activation inhibits OC differentiation and regulates bone turnover via PKA-dependent inhibition of NFκB nuclear translocation, suggesting a mechanism by which adenosine could target bone destruction in inflammatory diseases like rheumatoid arthritis.

Indexed as

AdenosineAdenosine A2 Receptor AgonistsAdenosine A2 Receptor AntagonistsAnimalsCell DifferentiationCell Line, TransformedCell NucleusCells, CulturedCyclic AMPCyclic AMP-Dependent Protein Kinase Catalytic SubunitsDown-RegulationFemaleGene Expression RegulationGene SilencingMAP Kinase Signaling SystemMiceAdenosineAdenosine A2 Receptor AgonistsAdenosine A2 Receptor AntagonistsCyclic AMPCyclic AMP-Dependent Protein Kinase Catalytic SubunitsNF-kappa B p50 SubunitNfkb1 protein, mousePrkaca protein, mouseProtein Kinase InhibitorsReceptor, Adenosine A2ARela protein, mouseTranscription Factor RelA

Identifiers

PMID23647065
PMCPMC3831714
OpenAlexW1575977354

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.