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

Singbrant, Sofie LU ; Russell, M. R.; Jovic, T.; Liddicoat, B.; Izon, D. J.; Purton, L. E.; Sims, N. A.; Martin, T. J.; Sankaran, V. G. and Walkley, C. R. (2011) In Blood 117(21). p.42-5631
Abstract
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... (More)
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. (Less)
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subject
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
in
Blood
volume
117
issue
21
pages
42 - 5631
publisher
American Society of Hematology
external identifiers
  • scopus:79957586600
ISSN
1528-0020
DOI
10.1182/blood-2010-11-320564
language
English
LU publication?
no
id
64ca0ab2-04db-4e6c-a587-535e8276400a (old id 8594828)
date added to LUP
2016-02-02 13:12:06
date last changed
2017-11-19 04:19:16
@article{64ca0ab2-04db-4e6c-a587-535e8276400a,
  abstract     = {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.},
  author       = {Singbrant, Sofie and Russell, M. R. and Jovic, T. and Liddicoat, B. and Izon, D. J. and Purton, L. E. and Sims, N. A. and Martin, T. J. and Sankaran, V. G. and Walkley, C. R.},
  issn         = {1528-0020},
  keyword      = {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},
  language     = {eng},
  number       = {21},
  pages        = {42--5631},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Erythropoietin couples erythropoiesis, B-lymphopoiesis, and bone homeostasis within the bone marrow microenvironment},
  url          = {http://dx.doi.org/10.1182/blood-2010-11-320564},
  volume       = {117},
  year         = {2011},
}