FGF-23 from erythroblasts promotes hematopoietic progenitor mobilization

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.



Work Title FGF-23 from erythroblasts promotes hematopoietic progenitor mobilization
Open Access
  1. Shinichi Ishii
  2. Tomohide Suzuki
  3. Kanako Wakahashi
  4. Noboru Asada
  5. Yuko Kawano
  6. Hiroki Kawano
  7. Akiko Sada
  8. Kentaro Minagawa
  9. Yukio Nakamura
  10. Seiya Mizuno
  11. Satoru Takahashi
  12. Toshimitsu Matsui
  13. Yoshio Katayama
License In Copyright (Rights Reserved)
Work Type Article
  1. Blood
Publication Date March 18, 2021
Publisher Identifier (DOI)
  1. https://doi.org/10.1182/blood.2020007172
Deposited July 19, 2021




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Work History

Version 1

  • Created
  • Added bloodbld2020007172.pdf
  • Added bloodbld2020010538c.pdf
  • Added Creator Shinichi Ishii
  • Added Creator Tomohide Suzuki
  • Added Creator Kanako Wakahashi
  • Added Creator Noboru Asada
  • Added Creator Yuko Kawano
  • Added Creator Hiroki Kawano
  • Added Creator Akiko Sada
  • Added Creator Kentaro Minagawa
  • Added Creator Yukio Nakamura
  • Added Creator Seiya Mizuno
  • Added Creator Satoru Takahashi
  • Added Creator Toshimitsu Matsui
  • Added Creator Yoshio Katayama
  • Published
  • Updated
  • Updated