FGF-23 from erythroblasts promotes hematopoietic progenitor mobilization

Abstract Fibroblast growth factor 23 (FGF-23) hormone is produced by bone-embedded osteocytes and regulates phosphate homeostasis in kidneys. We found that administration of granulocyte colony-stimulating (G-CSF) to mice induced a rapid, substantial increase FGF-23 messenger RNA bone marrow (BM) cells. This originated mainly from CD45−Ter119+CD71+ erythroblasts. protein BM extracellular fluid was markedly increased during G-CSF–induced hematopoietic progenitor cell (HPC) mobilization, but remained stable the blood, with no change level. Consistent hypoxia G-CSF, low oxygen concentration release human erythroblast HUDEP-2 cells vitro. The efficient mobilization G-CSF decreased drastically both FGF-23−/− chimeric deficiency, only cells, osteocyte-specific mice. finding suggests erythroblast-derived, not bone-derived, needed HPCs into circulation. Mechanistically, did influence CXCL-12 binding CXCR-4 on progenitors interfered their transwell migration toward CXCL-12, which canceled FGF receptor inhibitors. These results suggest erythroblasts facilitate HPC via production as an intrinsic suppressor chemoattraction.