The adenosine A2B receptor (ADORA2B) drives osteoclast-mediated bone resorption in hypoxia
Knowles H.
Osteoclast-mediated bone resorption is enhanced in the hypoxic microenvironment of diseases including rheumatoid arthritis and bone metastatic cancer. This increased resorption is driven by the hypoxia-inducible transcription factor, HIF. ADORA2b is a HIF-responsive gene that is upregulated in hypoxic osteoclasts. ADORA2b is only functional in hypoxia or inflammatory conditions, as only then are activating extracellular concentrations of adenosine achieved by hydrolysis of extracellular ATP. Given the increasing interest in musculoskeletal effects of extracellular ATP, we investigated whether ADORA2b plays a role in osteoclast-mediated resorption of bone.