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Erythropoietin mediated bone formation is regulated by mTOR signaling
Author(s) -
Kim Jinkoo,
Jung Younghun,
Sun Hongli,
Joseph Jeena,
Mishra Anjali,
Shiozawa Yusuke,
Wang Jingcheng,
Krebsbach Paul H.,
Taichman Russell S.
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23347
Subject(s) - erythropoietin , erythropoietin receptor , pi3k/akt/mtor pathway , microbiology and biotechnology , osteoclast , stromal cell , bone resorption , bone marrow , haematopoiesis , chemistry , mesenchymal stem cell , signal transduction , cancer research , endocrinology , biology , stem cell , immunology , receptor , biochemistry
Abstract 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 activates 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. J. Cell. Biochem. 113: 220–228, 2012. © 2011 Wiley Periodicals, Inc.