File:Model coupling hematopoiesis with osteopoiesis.jpg

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Coupling of hematopoiesis with osteopoiesis by Erythropoietin

Erythropoietin (Epo) is best known as a hematopoietic hormone. Epo is now known to have a number of non-hematpoietic roles. However, what is not clear is how the bone compartment recovers.

(A) Model of hematopoetic/osteopoiesis coupling by Epo. An acute bleed activates the kidney O2 sensors to secrete Epo. In the marrow, Epo activates hematopoietic stem cell (HSC) or progenitor cell (HPC) to enter the cycle (Green line), which results in the expansion of hematopoietic organ at the expense of the bone tissue by activating osteoclastogenesis. Ultimately, expansion of the hematopoietic organ leads to the restoration of the formed elements of the blood (Red lines). At the same time, Epo acts directly on mesenchymal stem cells (MSCs) and mixed bone marrow stromal cells (BMSCs) to induce bone formation. Ultimately, activation of MSCs and BMSCs results in the restoration of the bone tissues (Blue lines). In addition to the direct effects of Epo on HSCs, HPCs, and BMSCs, Epo activates HSCs and HPCs to secrete BMPs that target MSCs/BMSCs to reprogram the cells to differentiate into osteoblasts to regenerate the lost bone tissue. Moreover, the osteoblasts that are induced by Epo directly or indirectly support hematopoiesis as a bone marrow niche (Orange lines).

(B) Time plot graph of events activated by Epo. Elevation of circulating Epo levels (Purple line) facilitates expansion of the HSCs/HPCs to restore formed blood elements lost during an acute bleed (Green line), and to activate osteoclastogensis to expand the marrow cavity (Red line). At the same time Epo induces BMPs expression by HSCs/HPCs to promote bone formation indirectly (Orange line). At a later time, osteoblast number increases in the marrow stimulated directly by Epo's actions on MSCs/BMSCs and indirectly by BMPs secreted by HSCs/HPCs (Blue line). Together, Epo plays a critical and important role in cross talk between hematopoiesis and osteopoiesis by both direct and indirect pathways.

Figure 7. Journal.pone.0010853.g007.jpg


Yusuke Shiozawa, Younghun Jung, Anne M Ziegler, Elisabeth A Pedersen, Jianhua Wang, Zhuo Wang, Junhui Song, Jingcheng Wang, Clara H Lee, Sudha Sud, Kenneth J Pienta, Paul H Krebsbach, Russell S Taichman Erythropoietin couples hematopoiesis with bone formation. PLoS ONE: 2010, 5(5);e10853 PMID:20523730 | PLoS ONE

Citation: Shiozawa Y, Jung Y, Ziegler AM, Pedersen EA, Wang J, et al. (2010) Erythropoietin Couples Hematopoiesis with Bone Formation. PLoS ONE 5(5): e10853. doi:10.1371/journal.pone.0010853

Copyright: © 2010 Shiozawa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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current11:28, 27 February 2011Thumbnail for version as of 11:28, 27 February 2011486 × 600 (44 KB)S8600021 (Talk | contribs)===Coupling of hematopoiesis with osteopoiesis by Epo.== Erythropoietin (Epo) is best known as a hematopoietic hormone. Epo is now known to have a number of non-hematpoietic roles. However, what is not clear is how the bone compartment recovers. (A) Mo

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