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https://hdl.handle.net/2440/132322
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Type: | Journal article |
Title: | Tyrosine kinase receptor c-ros-oncogene 1 mediates TWIST-1 regulation of human mesenchymal stem cell lineage commitment |
Author: | Camp, E. Anderson, P.J. Zannettino, A.C.W. Gronthos, S. |
Citation: | Bone, 2017; 94:98-107 |
Publisher: | Elsevier |
Issue Date: | 2017 |
ISSN: | 8756-3282 1873-2763 |
Statement of Responsibility: | Esther Camp, Peter J. Anderson, Andrew C.W. Zannettino, Stan Gronthos |
Abstract: | The TWIST-1 gene encodes a basic helix-loop-helix (bHLH) transcription factor important in mediating skeletal and head mesodermal tissue development. Bone marrow-derived mesenchymal stem/ stromal cells (BMSC), express high levels of TWIST-1, which is down regulated during ex vivo expansion. Cultured BMSC over-expressing TWIST-1 display decreased capacity for osteogenic differentiation and an enhanced capacity to undergo adipogenesis, suggesting that TWIST-1 is a mediator of lineage commitment. However, little is known regarding the mechanism(s) by which TWIST-1 mediates cell fate determination. In this study, microarray analysis was used to identify a novel downstream TWIST-1 target, tyrosine kinase receptor c-ros-oncogene 1 (C-ROS-1), which was down regulated in TWIST-1 over-expressing BMSC. Chromatin immunoprecipitation analysis showed that TWIST-1 directly bound to two E-box binding sites on the proximal C-ROS-1 promoter. Knock-down of C-ROS-1 in human BMSC and cranial bone cells resulted in a decreased capacity for osteogenic differentiation in vitro. Conversely, suppression of C-ROS-1 in BMSC resulted in an enhanced capacity to undergo adipogenesis. Furthermore, reduced C-ROS-1 levels led to activation of different components of the PI3K/AKT/mTORC1 signalling pathway during osteogenic and adipogenic differentiation. Collectively, these data suggest that C-ROS-1 is involved in BMSC fate switching between osteogenesis and adipogenesis, mediated via PI3K/AKT/mTORC1 signalling. |
Keywords: | Mesenchymal stem cells; bone marrow stromal cells; TWIST-1; C-ROS-1; PI3K/AKT/mTOR signalling |
Rights: | © 2016 Elsevier Inc. All rights reserved. |
DOI: | 10.1016/j.bone.2016.09.019 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1046053 http://purl.org/au-research/grants/nhmrc/1042677 |
Published version: | http://dx.doi.org/10.1016/j.bone.2016.09.019 |
Appears in Collections: | Medicine publications |
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