Dysregulation of ectonucleotidase-mediated extracellular adenosine during postmenopausal bone loss

Stimulation of the A2BR receptor can compensate for decreased extracellular adenosine and attenuate bone loss. Adenosine and its receptors play a key role in bone homeostasis and regeneration. Extracellular adenosine is generated from CD39 and CD73 activity in the cell membrane, through conversion of adenosine triphosphate to adenosine monophosphate (AMP) and AMP to adenosine, respectively. Despite the relevance of CD39/CD73 to bone health, the roles of these enzymes in bona fide skeletal disorders remain unknown. We demonstrate that CD39/CD73 expression and extracellular adenosine levels in the bone marrow are substantially decreased in animals with osteoporotic bone loss. Knockdown of estrogen receptors ESR1 and ESR2 in primary osteoprogenitors and osteoclasts undergoing differentiation showed decreased coexpression of membrane-bound CD39 and CD73 and lower extracellular adenosine. Targeting the adenosine A2B receptor using an agonist attenuated bone loss in ovariectomized mice. Together, these findings suggest a pathological association of purine metabolism with estrogen deficiency and highlight the potential of A2B receptor as a target to treat osteoporosis.

• Publication year

  2019

• Venue

  Science Advances

• Publication date

  2019-08-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1126/sciadv.aax1387PMID 31457100PMCID 6703860
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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