Journal article
Erythropoietin mediated bone formation is regulated by mTOR signaling
Journal of cellular biochemistry, Vol.113(1), pp.220-228
01/01/2012
DOI: 10.1002/jcb.23347
PMCID: PMC3237787
PMID: 21898543
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: 220228, 2012. (C) 2011 Wiley Periodicals, Inc.
Details
- Title: Subtitle
- Erythropoietin mediated bone formation is regulated by mTOR signaling
- Creators
- Jinkoo Kim - University of MichiganYounghun Jung - University of MichiganHongli Sun - University of MichiganJeena Joseph - University of MichiganAnjali Mishra - University of MichiganYusuke Shiozawa - University of MichiganJingcheng Wang - University of MichiganPaul H. Krebsbach - University of MichiganRussell S. Taichman - University of Michigan
- Resource Type
- Journal article
- Publication Details
- Journal of cellular biochemistry, Vol.113(1), pp.220-228
- DOI
- 10.1002/jcb.23347
- PMID
- 21898543
- PMCID
- PMC3237787
- NLM abbreviation
- J Cell Biochem
- ISSN
- 0730-2312
- eISSN
- 1097-4644
- Publisher
- Wiley
- Number of pages
- 9
- Grant note
- RC1DE020721 / NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) PC073952 / Department of Defense; United States Department of Defense DK082481; DE020721; 1RC1DE020721; CA141426; CA093900 / National Institutes of health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R21CA141426 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01DK082481 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
- Language
- English
- Date published
- 01/01/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Craniofacial Anomalies Research Center; Oral and Maxillofacial Surgery
- Record Identifier
- 9984367743002771
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