FGF-23 from erythroblasts promotes hematopoietic progenitor mobilization

• Published in: Blood Vol. 137; no. 11; pp. 1457 - 1467
• Main Authors: Ishii, Shinichi, Suzuki, Tomohide, Wakahashi, Kanako, Asada, Noboru, Kawano, Yuko, Kawano, Hiroki, Sada, Akiko, Minagawa, Kentaro, Nakamura, Yukio, Mizuno, Seiya, Takahashi, Satoru, Matsui, Toshimitsu, Katayama, Yoshio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.03.2021
• Subjects: Animals; Cells, Cultured; Erythroblasts - cytology; Erythroblasts - metabolism; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Hematopoiesis; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Humans; Male; Mice; Mice, Inbred C57BL; RNA, Messenger - genetics; Up-Regulation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2020007172

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