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Cited by 133Adenosine and Purinergic SignalingBone Metabolism and DiseasesAlkaline Phosphatase Research Studies

Adenosine and bone metabolism

Open access
Mediero, Aránzazu, Cronstein, Bruce N.·2013·Trends in Endocrinology & Metabolism
DOI 10.1016/j.tem.2013.02.001PMC PMC3669669
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Abstract

Bone is a dynamic organ that undergoes continuous remodeling while maintaining a balance between bone formation and resorption. Osteoblasts, which synthesize and mineralize new bone, and osteoclasts, the cells that resorb bone, act in concert to maintain bone homeostasis. In recent years, there has been increasing appreciation of purinergic regulation of bone metabolism. Adenosine, released locally, mediates its physiologic and pharmacologic actions via interactions with G protein-coupled receptors, and recent work has indicated that these receptors are involved in the regulation of osteoclast differentiation and function, as well as in osteoblast differentiation and bone formation. Moreover, adenosine receptors also regulate chondrocyte and cartilage homeostasis. These recent findings underscore the potential therapeutic importance of adenosine receptors in regulating bone physiology and pathology.

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  • In vitro and animal models, antagonism of A2A receptors influenced by caffeine promotes osteoclast formation and function, while antagonism of A2B receptors inhibits osteoblast formation.

    “In vitro and animal models, antagonism of A2A receptors influenced by caffeine promotes osteoclast formation and function, while antagonism of A2B receptors inhibits osteoblast formation [41].”

    From Association between caffeine consumption and bone mineral density in children and adolescent: Observational and Mendelian randomization study (2023) · cites this paper as [41]

    The osteoclast-metabolism section reports that A2A receptor activation inhibits osteoclast differentiation and function, and that A2A-deficient mice have more osteoclasts. The osteoblast-metabolism section reports that A2B blockade prevents an agonist-induced increase in osteoblast differentiation. The paper identifies caffeine as an adenosine-receptor antagonist, but does not report that caffeine itself produced these bone-cell effects; it also notes a contrasting finding for A2A stimulation in human osteoclast precursors. (LLM, conf=0.82)

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  • A major mechanism of caffeine in organs is its direct and indirect effects on bone metabolism through competitive inhibition of four adenosine receptors (A1, A2A, A2B, A3), which are expressed in undifferentiated osteoblast precursors and differentiated osteoblasts.

    “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 [41]

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Sorted by citations

Authors
Mediero, A., & Cronstein, B. N.
Affiliations
NYU Langone Health (US)
ORCID
Venue
Trends in Endocrinology & Metabolism
Publisher
Elsevier BV
Published
2013-06
Volume
24
Issue
6
Pages
290-300
ISSN
1043-2760 (ISSN-L)
DOI
10.1016/j.tem.2013.02.001
PMC
PMC3669669
OpenAlex
W2163693480
Cited by
133
References
3
Citations by year
2026: 9 · 2025: 9 · 2024: 8 · 2023: 14 · 2022: 11 · 2021: 16 · 2020: 11 · 2019: 13 · 2018: 10 · 2017: 11 · 2016: 9 · 2015: 5 · 2014: 7
FWCI
0.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Trends in Endocrinology and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Gilead Sciences
  • National Institutes of Health (UL1TR000038)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR046121, AR-56672, R01AR041911, R56AR056672, R01AR054897, AR 54897, P30AR046121, R01AR056672)
  • National Center for Advancing Translational Sciences
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
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
Keywords
adenosine, bone metabolism, purinergic signaling, adenosine receptors, G protein-coupled receptors, osteoclastogenesis, osteogenic differentiation, bone remodeling, bone homeostasis, chondrocyte homeostasis, cartilage homeostasis
MeSH terms
Adenosine, Animals, Bone Resorption, Humans, Osteogenesis, Receptors, Purinergic P1, Chondrocytes

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