TY - JOUR
T1 - Erythropoietin couples hematopoiesis with bone formation
AU - Shiozawa, Yusuke
AU - Jung, Younghun
AU - Ziegler, Anne M.
AU - Pedersen, Elisabeth A.
AU - Wang, Jianhua
AU - Wang, Zhuo
AU - Song, Junhui
AU - Wang, Jingcheng
AU - Lee, Clara H.
AU - Sud, Sudha
AU - Pienta, Kenneth J.
AU - Krebsbach, Paul H.
AU - Taichman, Russell S.
PY - 2010
Y1 - 2010
N2 - Background: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. Methodology/Principal Findings: 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. Conclusions/Significance: 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 hematopoesis and osteopoiesis in the marrow.
AB - Background: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. Methodology/Principal Findings: 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. Conclusions/Significance: 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 hematopoesis and osteopoiesis in the marrow.
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U2 - 10.1371/journal.pone.0010853
DO - 10.1371/journal.pone.0010853
M3 - Article
C2 - 20523730
AN - SCOPUS:77956509034
SN - 1932-6203
VL - 5
JO - PloS one
JF - PloS one
IS - 5
M1 - e10853
ER -