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Title: 0628 - Mechanical Strain Regulates Mesenchymal Stem Cell Activation Through Meditating Autophagy

Authors:

Portia Grayson (Presenter)
Peninsula School of Dentistry, University of Plymouth

Kai Yang, School of Stomatology, Capital Medical University
Louise Belfield, Peninsula School of Dentistry, University of Plymouth
Yan Gao, School of Stomatology, Capital Medical University
Christopher Tredwin, Peninsula School of Dentistry, University of Plymouth
Bing Hu, Peninsula School of Dentistry, University of Plymouth

Abstract:

Objectives: Mesenchymal stem cells (MSCs) are able to differentiate into a multitude of cell types in adult tissue, including the osteoblasts of bone. The activation and differentiation of these stem cells is controlled by specific cues which may be molecular or mechanical. Cells are subjected to mechanical strain as a part of normal biological processes as well as by external intervention, such as in tooth movement for orthodontic purposes. However, much is still unknown of the mechanisms involved in MSC activation following exposure to mechanical strain. This study aimed to elucidate the molecular mechanisms involved in MSCs differentiation down the osteogenic lineage, on exposure to mechanical strain.

Methods: A fixed orthodontic appliance induced rat first lower molar tooth movement model at sequential stages was analysed for the expression of osteogenesis and autophagy markers using immunofluorescence analysis. In vitro, MSCs derived from human bone marrow were exposed to constant tensile strain at different time points and analysed for the expression of molecules involved in osteogenesis and autophagy, using real time RT-PCR and western blotting. The autophagy status was chemically modulated using specific inhibitors or activators. Key autophagy genes were silenced using a tetracycline controlled system. A tamoxifen mediated autophagy inhibition system was used to investigate the molecular role of autophagy.

Results: Osteogenesis marker genes, RUNX2 and DMP1, were expressed around the periodontal ligament and alveolar bone in the area of the teeth exposed to tensile strain, where LC3 positive autophagosomes also accumulated. The osteogenic marker expression in MSCs exposed to strain is controlled by the autophagy pathway, and linked with intracellular autophagosome status.

Conclusions: Our data suggests that constant tensile strain can cause MSC activation and osteogenic differentiation, when autophagy is modulated.

This abstract is based on research that was funded entirely or partially by an outside source:
The authors thank National Natural Science Foundation of China to K.Y. (81771103), the Oral and Dental Research Trust GSK award to L.A.B. and the European Union Marie Skłodowska-Curie actions (618930, OralStem FP7-PEOPLE-2013-CIG), the European Regional Development Fund and the Biotechnology and Biological Sciences Research Council of the UK (BB/L02392X/1) to B.H.

Disclosure Statement:
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE

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