Erythropoietin couples hematopoiesis with bone formation.

<h4>Background</h4>It is well established that bleeding activates the hematopoietic system to regenerate the loss of mature blood elements. We have shown that hematopoietic stem cells (HSCs) isolated from animals challenged with an acute bleed regulate osteoblast differentiation from mar...

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Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-05-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0010853&type=printable
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author 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
author_facet 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
author_sort Yusuke Shiozawa
collection DOAJ
description <h4>Background</h4>It is well established that bleeding activates the hematopoietic system to regenerate the loss of mature blood elements. We have shown that hematopoietic stem cells (HSCs) isolated from animals challenged with an acute bleed regulate osteoblast differentiation from marrow stromal cells. This suggests that HSCs participate in bone formation where the molecular basis for this activity is the production of BMP2 and BMP6 by HSCs. Yet, what stimulates HSCs to produce BMPs is unclear.<h4>Methodology/principal findings</h4>In this study, we demonstrate that erythropoietin (Epo) activates Jak-Stat signaling pathways in HSCs which leads to the production of BMPs. Critically, Epo also directly activates mesenchymal cells to form osteoblasts in vitro, which in vivo leads to bone formation. Importantly, Epo first activates osteoclastogenesis which is later followed by osteoblastogenesis that is induced by either Epo directly or the expression of BMPs by HSCs to form bone.<h4>Conclusions/significance</h4>These data for the first time demonstrate that Epo regulates the formation of bone by both direct and indirect pathways, and further demonstrates the exquisite coupling between hematopoiesis and osteopoiesis in the marrow.
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spelling doaj-art-8a130f813fb94deaa1d3cd0f1c917bc42025-08-20T03:07:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-05-0155e1085310.1371/journal.pone.0010853Erythropoietin couples hematopoiesis with bone formation.Yusuke ShiozawaYounghun JungAnne M ZieglerElisabeth A PedersenJianhua WangZhuo WangJunhui SongJingcheng WangClara H LeeSudha SudKenneth J PientaPaul H KrebsbachRussell S Taichman<h4>Background</h4>It is well established that bleeding activates the hematopoietic system to regenerate the loss of mature blood elements. We have shown that hematopoietic stem cells (HSCs) isolated from animals challenged with an acute bleed regulate osteoblast differentiation from marrow stromal cells. This suggests that HSCs participate in bone formation where the molecular basis for this activity is the production of BMP2 and BMP6 by HSCs. Yet, what stimulates HSCs to produce BMPs is unclear.<h4>Methodology/principal findings</h4>In this study, we demonstrate that erythropoietin (Epo) activates Jak-Stat signaling pathways in HSCs which leads to the production of BMPs. Critically, Epo also directly activates mesenchymal cells to form osteoblasts in vitro, which in vivo leads to bone formation. Importantly, Epo first activates osteoclastogenesis which is later followed by osteoblastogenesis that is induced by either Epo directly or the expression of BMPs by HSCs to form bone.<h4>Conclusions/significance</h4>These data for the first time demonstrate that Epo regulates the formation of bone by both direct and indirect pathways, and further demonstrates the exquisite coupling between hematopoiesis and osteopoiesis in the marrow.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0010853&type=printable
spellingShingle 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
title Erythropoietin couples hematopoiesis with bone formation.
title_full Erythropoietin couples hematopoiesis with bone formation.
title_fullStr Erythropoietin couples hematopoiesis with bone formation.
title_full_unstemmed Erythropoietin couples hematopoiesis with bone formation.
title_short Erythropoietin couples hematopoiesis with bone formation.
title_sort erythropoietin couples hematopoiesis with bone formation
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0010853&type=printable
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