Dysregulation of ectonucleotidase-mediated extracellular adenosine during postmenopausal bone loss.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Shih, Y-RV; Liu, M; Kwon, SK; Iida, M; Gong, Y; Sangaj, N; Varghese, S

Published Date

  • August 2019

Published In

Volume / Issue

  • 5 / 8

Start / End Page

  • eaax1387 -

PubMed ID

  • 31457100

Pubmed Central ID

  • 31457100

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.aax1387

Language

  • eng

Conference Location

  • United States