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TGF beta 1-induced recruitment of human bone mesenchymal stem cells is mediated by the primary cilium in a SMAD3-dependent manner
Date
2016
Abstract
The recruitment of mesenchymal stem cells (MSCs) is a crucial process in the development, maintenance and repair of tissues throughout the body. Transforming growth factor-β1 (TGFβ1) is a potent chemokine essential for the recruitment of MSCs in bone, coupling the remodelling cycle. The primary cilium is a sensory organelle with important roles in bone and has been associated with cell migration and more recently TGFβ signalling. Dysregulation of TGFβ signalling or cilia has been linked to a number of skeletal pathologies. Therefore, this study aimed to determine the role of the primary cilium in TGFβ1 signalling and associated migration in human MSCs. In this study we demonstrate that low levels of TGFβ1 induce the recruitment of MSCs, which relies on proper formation of the cilium. Furthermore, we demonstrate that receptors and downstream signalling components in canonical TGFβ signalling localize to the cilium and that TGFβ1 signalling is associated with activation of SMAD3 at the ciliary base. These findings demonstrate a novel role for the primary cilium in the regulation of TGFβ signalling and subsequent migration of MSCs, and highlight the cilium as a target to manipulate this key pathway and enhance MSC recruitment for the treatment of skeletal diseases.
Supervisor
Description
peer-reviewed
Publisher
Nature Publishing Group
Citation
Scientific Reports;6: 35542
Collections
Files
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Hoey_2016_induced.pdf
Adobe PDF, 1.4 MB
Funding code
Funding Information
European Research Council (ERC), Science Foundation Ireland (SFI)
Sustainable Development Goals
External Link
Type
Article
Rights
https://creativecommons.org/licenses/by-nc-sa/1.0/