Erythropoietin couples hematopoiesis with bone formation.
Erythropoietin couples hematopoiesis with bone formation.
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DOI：
10.1371/journal.pone.0010853
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发表时间：
2010-05-27
期刊：
影响因子：
3.7
通讯作者：
Taichman RS
中科院分区：
文献类型：
--
作者：
Shiozawa Y;Jung Y;Ziegler AM;Pedersen EA;Wang J;Wang Z;Song J;Wang J;Lee CH;Sud S;Pienta KJ;Krebsbach PH;Taichman RS
众所周知，出血激活了造血系统，使成熟血液成分的损失得以再生。我们已经证明，从急性出血攻击的动物中分离的造血干细胞(HSCs)可以调节骨髓基质细胞向成骨细胞的分化。这表明，HSCs参与骨形成，而这种活动的分子基础是HSCs产生BMP2和Bmp6。然而，是什么刺激HSC产生BMP尚不清楚。在这项研究中，我们证明了促红细胞生成素(EPO)激活了HSCs中的Jak-Stat信号通路，从而导致BMP的产生。关键的是，EPO还在体外直接激活间充质细胞形成成骨细胞，在体内导致成骨。重要的是，EPO首先激活破骨细胞生成，然后由EPO直接诱导成骨细胞生成，或由HSCs表达BMPs成骨。这些数据首次表明，EPO通过直接和间接途径调节骨的形成，并进一步证明了骨髓中造血和成骨之间的精细耦合。
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. 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. 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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影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
DOI：
10.1073/pnas.1031753100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Erbayraktar, S;Grasso, G;Brines, M
通讯作者：
Brines, M
影响因子：
17.3
作者：
Goddard, JC
通讯作者：
Goddard, JC
影响因子：
4.8
作者：
GAZIT, D;KARMISH, M;BAB, I
通讯作者：
BAB, I
影响因子：
6.2
作者：
Gurevitch, O;Prigozhina, TB;Slavin, S
通讯作者：
Slavin, S