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Erythropoietin modulates bone marrow stromal cell differentiation

Erythropoietin is essential for bone marrow erythropoiesis and erythropoietin receptor on non-erythroid cells including bone marrow stromal cells suggests systemic effects of erythropoietin. Tg6 mice with chronic erythropoietin overexpression have a high hematocrit, reduced trabecular and cortical b...

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Autores principales: Suresh, Sukanya, de Castro, Luis Fernandez, Dey, Soumyadeep, Robey, Pamela G., Noguchi, Constance Tom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804931/
https://www.ncbi.nlm.nih.gov/pubmed/31666996
http://dx.doi.org/10.1038/s41413-019-0060-0
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author Suresh, Sukanya
de Castro, Luis Fernandez
Dey, Soumyadeep
Robey, Pamela G.
Noguchi, Constance Tom
author_facet Suresh, Sukanya
de Castro, Luis Fernandez
Dey, Soumyadeep
Robey, Pamela G.
Noguchi, Constance Tom
author_sort Suresh, Sukanya
collection PubMed
description Erythropoietin is essential for bone marrow erythropoiesis and erythropoietin receptor on non-erythroid cells including bone marrow stromal cells suggests systemic effects of erythropoietin. Tg6 mice with chronic erythropoietin overexpression have a high hematocrit, reduced trabecular and cortical bone and bone marrow adipocytes, and decreased bone morphogenic protein 2 driven ectopic bone and adipocyte formation. Erythropoietin treatment (1 200 IU·kg(–1)) for 10 days similarly exhibit increased hematocrit, reduced bone and bone marrow adipocytes without increased osteoclasts, and reduced bone morphogenic protein signaling in the bone marrow. Interestingly, endogenous erythropoietin is required for normal differentiation of bone marrow stromal cells to osteoblasts and bone marrow adipocytes. ΔEpoR(E) mice with erythroid restricted erythropoietin receptor exhibit reduced trabecular bone, increased bone marrow adipocytes, and decreased bone morphogenic protein 2 ectopic bone formation. Erythropoietin treated ΔEpoR(E) mice achieved hematocrit similar to wild-type mice without reduced bone, suggesting that bone reduction with erythropoietin treatment is associated with non-erythropoietic erythropoietin response. Bone marrow stromal cells from wild-type, Tg6, and ΔEpoR(E)-mice were transplanted into immunodeficient mice to assess development into a bone/marrow organ. Like endogenous bone formation, Tg6 bone marrow cells exhibited reduced differentiation to bone and adipocytes indicating that high erythropoietin inhibits osteogenesis and adipogenesis, while ΔEpoR(E) bone marrow cells formed ectopic bones with reduced trabecular regions and increased adipocytes, indicating that loss of erythropoietin signaling favors adipogenesis at the expense of osteogenesis. In summary, endogenous erythropoietin signaling regulates bone marrow stromal cell fate and aberrant erythropoietin levels result in their impaired differentiation.
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spelling pubmed-68049312019-10-30 Erythropoietin modulates bone marrow stromal cell differentiation Suresh, Sukanya de Castro, Luis Fernandez Dey, Soumyadeep Robey, Pamela G. Noguchi, Constance Tom Bone Res Article Erythropoietin is essential for bone marrow erythropoiesis and erythropoietin receptor on non-erythroid cells including bone marrow stromal cells suggests systemic effects of erythropoietin. Tg6 mice with chronic erythropoietin overexpression have a high hematocrit, reduced trabecular and cortical bone and bone marrow adipocytes, and decreased bone morphogenic protein 2 driven ectopic bone and adipocyte formation. Erythropoietin treatment (1 200 IU·kg(–1)) for 10 days similarly exhibit increased hematocrit, reduced bone and bone marrow adipocytes without increased osteoclasts, and reduced bone morphogenic protein signaling in the bone marrow. Interestingly, endogenous erythropoietin is required for normal differentiation of bone marrow stromal cells to osteoblasts and bone marrow adipocytes. ΔEpoR(E) mice with erythroid restricted erythropoietin receptor exhibit reduced trabecular bone, increased bone marrow adipocytes, and decreased bone morphogenic protein 2 ectopic bone formation. Erythropoietin treated ΔEpoR(E) mice achieved hematocrit similar to wild-type mice without reduced bone, suggesting that bone reduction with erythropoietin treatment is associated with non-erythropoietic erythropoietin response. Bone marrow stromal cells from wild-type, Tg6, and ΔEpoR(E)-mice were transplanted into immunodeficient mice to assess development into a bone/marrow organ. Like endogenous bone formation, Tg6 bone marrow cells exhibited reduced differentiation to bone and adipocytes indicating that high erythropoietin inhibits osteogenesis and adipogenesis, while ΔEpoR(E) bone marrow cells formed ectopic bones with reduced trabecular regions and increased adipocytes, indicating that loss of erythropoietin signaling favors adipogenesis at the expense of osteogenesis. In summary, endogenous erythropoietin signaling regulates bone marrow stromal cell fate and aberrant erythropoietin levels result in their impaired differentiation. Nature Publishing Group UK 2019-07-25 /pmc/articles/PMC6804931/ /pubmed/31666996 http://dx.doi.org/10.1038/s41413-019-0060-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Suresh, Sukanya
de Castro, Luis Fernandez
Dey, Soumyadeep
Robey, Pamela G.
Noguchi, Constance Tom
Erythropoietin modulates bone marrow stromal cell differentiation
title Erythropoietin modulates bone marrow stromal cell differentiation
title_full Erythropoietin modulates bone marrow stromal cell differentiation
title_fullStr Erythropoietin modulates bone marrow stromal cell differentiation
title_full_unstemmed Erythropoietin modulates bone marrow stromal cell differentiation
title_short Erythropoietin modulates bone marrow stromal cell differentiation
title_sort erythropoietin modulates bone marrow stromal cell differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804931/
https://www.ncbi.nlm.nih.gov/pubmed/31666996
http://dx.doi.org/10.1038/s41413-019-0060-0
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