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Erythropoietin mediated bone formation is regulated by mTOR signaling

dc.contributor.authorKim, Jinkooen_US
dc.contributor.authorJung, Younghunen_US
dc.contributor.authorSun, Honglien_US
dc.contributor.authorJoseph, Jeenaen_US
dc.contributor.authorMishra, Anjalien_US
dc.contributor.authorShiozawa, Yusukeen_US
dc.contributor.authorWang, Jingchengen_US
dc.contributor.authorKrebsbach, Paul H.en_US
dc.contributor.authorTaichman, Russell S.en_US
dc.date.accessioned2012-01-05T22:07:03Z
dc.date.available2013-03-04T15:29:55Zen_US
dc.date.issued2012-01en_US
dc.identifier.citationKim, Jinkoo; Jung, Younghun; Sun, Hongli; Joseph, Jeena; Mishra, Anjali; Shiozawa, Yusuke; Wang, Jingcheng; Krebsbach, Paul H.; Taichman, Russell S. (2012). "Erythropoietin mediated bone formation is regulated by mTOR signaling." Journal of Cellular Biochemistry 113(1): 220-228. <http://hdl.handle.net/2027.42/89548>en_US
dc.identifier.issn0730-2312en_US
dc.identifier.issn1097-4644en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/89548
dc.description.abstractThe 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.en_US
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherOsteoblastsen_US
dc.subject.otherHSCsen_US
dc.subject.otherOsteoclastsen_US
dc.subject.otherErythropoietinen_US
dc.subject.otherMTORen_US
dc.subject.otherRapamycinen_US
dc.titleErythropoietin mediated bone formation is regulated by mTOR signalingen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelGeneticsen_US
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.subject.hlbtoplevelScienceen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michiganen_US
dc.contributor.affiliationumDepartment of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michiganen_US
dc.contributor.affiliationumDepartment of Periodontics & Oral Medicine, University of Michigan School of Dentistry, 1011 North University Ave., Ann Arbor, MI 48109‐1078.en_US
dc.identifier.pmid21898543en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/89548/1/23347_ftp.pdf
dc.identifier.doi10.1002/jcb.23347en_US
dc.identifier.sourceJournal of Cellular Biochemistryen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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