Erythropoietin and skeletal cells crosstalks in physiology and disease

The hypoxia-inducible factor 2alpha (HIF-2), which is a member of the HIF family of transcription factors and a critical component of the hypoxia-driven pathway, regulates adult erythropoiesis through the renal production and secretion of erythropoietin (EPO). Notably, circulating EPO also affects bone mass through either direct or indirect actions on osteoblastic and osteoclastic cells. Adding complexity to the picture, we have recently reported that osteoblastic cells produce and secrete EPO upon activation of HIF-2. Although physiological role of osteoblastic EPO in controlling hematopoiesis remains to be determined, our findings could have translational implications for the treatment of anemia.