Erythropoietin mediated bone formation is regulated by mTOR signaling
Article first published online: 9 DEC 2011
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 113, Issue 1, pages 220–228, January 2012
How to Cite
Kim, J., Jung, Y., Sun, H., Joseph, J., Mishra, A., Shiozawa, Y., Wang, J., Krebsbach, P. H. and Taichman, R. S. (2012), Erythropoietin mediated bone formation is regulated by mTOR signaling. J. Cell. Biochem., 113: 220–228. doi: 10.1002/jcb.23347
- Issue published online: 9 DEC 2011
- Article first published online: 9 DEC 2011
- Accepted manuscript online: 6 SEP 2011 12:11PM EST
- Manuscript Accepted: 29 AUG 2011
- Manuscript Received: 25 AUG 2011
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.