Erythropoietin mediated bone formation is regulated by mTOR signaling.
Erythropoietin mediated bone formation is regulated by mTOR signaling.
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促红细胞生成素介导的骨形成受 mTOR 信号传导调节。
DOI：
10.1002/jcb.23347
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发表时间：
2012-01
影响因子：
4
通讯作者：
Taichman, Russell S.
中科院分区：
文献类型：
--
作者：
Kim, Jinkoo;Jung, Younghun;Sun, Hongli;Joseph, Jeena;Mishra, Anjali;Shiozawa, Yusuke;Wang, Jingcheng;Krebsbach, Paul H.;Taichman, Russell S.
红细胞生成素（Epo）和Epo/Epo受体（EpoR）信号传导途径在红细胞产生中的作用已得到充分确立。然而，关于非造血细胞中的Epo/EpoR信号传导知之甚少。最近，我们证明了Epo激活造血干细胞（HSC）中的JAK/STAT信号，导致骨形态发生蛋白2（BMP 2）的产生和骨形成，并且Epo还直接激活间充质细胞以在体外形成成骨细胞。在这项研究中，我们研究了mTOR信号传导对Epo介导的成骨细胞和破骨细胞生成的影响。我们发现雷帕霉素对mTOR的抑制分别阻断了人骨髓基质细胞（hBMSC）和ST 2细胞中Epo依赖性和非依赖性的成骨细胞表型。此外，我们发现雷帕霉素抑制小鼠骨髓单个核细胞和Raw 264.7细胞中Epo依赖性和非依赖性破骨细胞生成。最后，我们证明，促红细胞生成素增加NFATc 1的表达和减少组织蛋白酶K的表达，在mTOR-独立的方式，导致破骨细胞数量的增加和吸收活性的降低。总之，这些结果强烈表明mTOR信号传导在Epo介导的骨稳态中起重要作用。
The role of erythropoietin (Epo) and Epo/Epo receptor (EpoR) signaling pathways for production of red blood cells are well established. However, little is known about Epo/EpoR signaling in non-hematopoietic cells. Recently, we demonstrated that Epo activates JAK/STAT signaling in hematopoietic stem cells (HSCs), leading to the production of bone morphogenetic protein 2 (BMP2) and bone formation and that Epo also directly activate mesenchymal cells to form osteoblasts in vitro. In this study, we investigated the effects of mTOR signaling on Epo-mediated osteoblastogenesis and osteoclastogenesis. We found that mTOR inhibition by rapamycin blocks Epo-dependent and -independent osteoblastic phenotypes in human bone marrow stromal cells (hBMSCs) and ST2 cells, respectively. Furthermore, we found that rapamycin inhibits Epo-dependent and -independent osteoclastogenesis in mouse bone marrow mononuclear cells and Raw264.7 cells. Finally, we demonstrated that Epo increases NFATc1 expression and decreases cathepsin K expression in an mTOR-independent manner, resulting in an increase of osteoclast numbers and a decrease in resorption activity. Taken together, these results strongly indicate that mTOR signaling plays an important role in Epo-mediated bone homeostasis.
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影响因子：
1.7
作者：
Isomoto, Shinji;Hattori, Koji;Takakura, Yoshinori
通讯作者：
Takakura, Yoshinori
DOI：
10.1073/pnas.0630444100
发表时间：
2003-04-15
影响因子：
11.1
作者：
Calvillo, L;Latini, R;Brines, M
通讯作者：
Brines, M
DOI：
10.1056/nejmoa1005361
发表时间：
2010-12-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bashutski JD;Eber RM;Kinney JS;Benavides E;Maitra S;Braun TM;Giannobile WV;McCauley LK
通讯作者：
McCauley LK
影响因子：
4
作者：
Lee, Kyu-Won;Yook, Jin-Yong;Cho, Yee Sook
通讯作者：
Cho, Yee Sook
影响因子：
12.4
作者：
Glantschnig, H;Fisher, JE;Reszka, AA
通讯作者：
Reszka, AA