Gene interactions and pathways from curated databases and text-mining
J Cell Biochem 2012, PMID: 21898543

Erythropoietin mediated bone formation is regulated by mTOR signaling.

Kim, Jinkoo; Jung, Younghun; Sun, Hongli; Joseph, Jeena; Mishra, Anjali; Shiozawa, Yusuke; Wang, Jingcheng; Krebsbach, Paul H; Taichman, Russell S

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.

Document information provided by NCBI PubMed

Text Mining Data

mTOR signaling — Erythropoietin: " Erythropoietin mediated bone formation is regulated by mTOR signaling "

JAK/STAT → Epo: " 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 "

JAK/STAT → Epo: " 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 "

JAK/STAT → Epo: " 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 "

JAK/STAT → Epo: " 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 "

Manually curated Databases

No curated data.