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Erythropoietin couples erythropoiesis, B-lymphopoiesis, and bone homeostasis within the bone marrow microenvironment

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Author

  • Sofie Singbrant
  • M. R. Russell
  • T. Jovic
  • B. Liddicoat
  • D. J. Izon
  • L. E. Purton
  • N. A. Sims
  • T. J. Martin
  • V. G. Sankaran
  • C. R. Walkley

Summary, in English

Erythropoietin (Epo) has been used in the treatment of anemia resulting from numerous etiologies, including renal disease and cancer. However, its effects are controversial and the expression pattern of the Epo receptor (Epo-R) is debated. Using in vivo lineage tracing, we document that within the hematopoietic and mesenchymal lineage, expression of Epo-R is essentially restricted to erythroid lineage cells. As expected, adult mice treated with a clinically relevant dose of Epo had expanded erythropoiesis because of amplification of committed erythroid precursors. Surprisingly, we also found that Epo induced a rapid 26% loss of the trabecular bone volume and impaired B-lymphopoiesis within the bone marrow microenvironment. Despite the loss of trabecular bone, hematopoietic stem cell populations were unaffected. Inhibition of the osteoclast activity with bisphosphonate therapy blocked the Epo-induced bone loss. Intriguingly, bisphosphonate treatment also reduced the magnitude of the erythroid response to Epo. These data demonstrate a previously unrecognized in vivo regulatory network coordinating erythropoiesis, B-lymphopoiesis, and skeletal homeostasis. Importantly, these findings may be relevant to the clinical application of Epo.

Publishing year

2011

Language

English

Pages

42-5631

Publication/Series

Blood

Volume

117

Issue

21

Document type

Journal article

Publisher

American Society of Hematology

Topic

  • Hematology

Keywords

  • Male
  • Lymphopoiesis/*physiology
  • Humans
  • *Homeostasis
  • Gene Expression
  • Flow Cytometry
  • Erythropoietin/*pharmacology
  • Erythropoiesis/*physiology
  • Erythroblasts/metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Cultured
  • Cells
  • Bone and Bones/*metabolism
  • Bone Remodeling/physiology
  • Bone Marrow/*drug effects/metabolism
  • Animals
  • B-Lymphocytes/*metabolism
  • Mesoderm/cytology/metabolism
  • Mice
  • Inbred C57BL
  • Receptors
  • Erythropoietin/metabolism
  • Recombinant Proteins
  • Spleen/cytology/metabolism

Status

Published

ISBN/ISSN/Other

  • ISSN: 1528-0020