Mechanical stress affects methylation pattern of GNAS isoforms and osteogenic differentiation of hAT-MSCs.

Autor: Vlaikou AM; Laboratory of Biology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Greece., Kouroupis D; Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas (FORTH), Ioannina 45110, Greece; Laboratory of Biological Chemistry, Medical Faculty, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece., Sgourou A; Laboratory of Biology, School of Science and Technology, Hellenic Open University, Patras 26222, Greece., Markopoulos GS; Laboratory of Biology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Greece; Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas (FORTH), Ioannina 45110, Greece; Laboratory of Biological Chemistry, Medical Faculty, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece., Bagli E; Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas (FORTH), Ioannina 45110, Greece; Laboratory of Biological Chemistry, Medical Faculty, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece., Markou M; Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas (FORTH), Ioannina 45110, Greece; Laboratory of Biological Chemistry, Medical Faculty, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece., Papadopoulou Z; Laboratory of Biology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Greece., Fotsis T; Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas (FORTH), Ioannina 45110, Greece; Laboratory of Biological Chemistry, Medical Faculty, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece., Nakos G; Department of Intensive Care Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Greece., Lekka ME; Laboratory of Biochemistry, Department of Chemistry, School of Sciences, University of Ioannina, 45110, Greece. Electronic address: mlekka@uoi.gr., Syrrou M; Laboratory of Biology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110, Greece. Electronic address: msyrrou@cc.uoi.gr.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2017 Aug; Vol. 1864 (8), pp. 1371-1381. Date of Electronic Publication: 2017 May 05.
DOI: 10.1016/j.bbamcr.2017.05.005
Abstrakt: Mechanical stress exerts a substantial role on skeletal-cell renewal systems, whereas accumulating evidence suggests that epigenetic mechanisms induce changes and differential gene expression. Although the underlying mechanisms remain to be fully elucidated, our study suggests that the influence of the long term mechanical stimulation elicits epigenetic modifications controlling osteogenic differentiation of human adipose tissue multipotential stromal cells (hAT-MSCs) and contributes to an accelerating in vitro osteogenesis. GNAS imprinting gene acts as a critical regulator of osteoblast differentiation and is implicated in human genetic disorders with pathological formation of ectopic-skeletal bone. Investigating a wide variety of stimuli, we showed that daily mechanical stretch on hAT-MSCs of 7th and 15th days' intervals induced a significant down-regulation in DNA methylation status of critical CpG sites of NESP and GNASXL isoforms, accompanied by up-regulation of the corresponding gene transcripts, and osteogenic differentiation earlier in culture. Importantly, methylation analysis of differentiating bone marrow-derived MSCs revealed similar methylation patterns. Bioinformatic analysis further showed that all CpG islands exhibiting significant methylation alterations encompassed transcriptional repressor CTCF binding sites. We hereby emphasize the need to investigate the epigenetic alterations on hAT-MSCs during environmental mechanical forces and to consider how the knowledge gained through these studies may foster new means of symptoms prevention and management of ectopic bone formation in the clinic.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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