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

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 h...

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Bibliographic Details
Published in:Blood 2011-05, Vol.117 (21), p.5631-5642
Main Authors: Singbrant, Sofie, Russell, Megan R., Jovic, Tanja, Liddicoat, Brian, Izon, David J., Purton, Louise E., Sims, Natalie A., Martin, T. John, Sankaran, Vijay G., Walkley, Carl R.
Format: Article
Language:English
Subjects:
Animals
B-Lymphocytes - metabolism
Biological and medical sciences
Bone and Bones - metabolism
Bone Marrow - drug effects
Bone Marrow - metabolism
Bone Remodeling - physiology
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Erythroblasts - metabolism
Erythropoiesis - physiology
Erythropoietin - pharmacology
Flow Cytometry
Gene Expression
Hematologic and hematopoietic diseases
Homeostasis
Humans
Lymphopoiesis - physiology
Male
Medical sciences
Mesoderm - cytology
Mesoderm - metabolism
Mice
Mice, Inbred C57BL
Receptors, Erythropoietin - metabolism
Recombinant Proteins
Spleen - cytology
Spleen - metabolism
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2010-11-320564