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Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model

Trauma-induced heterotopic ossification is an intriguing phenomenon involving the inappropriate ossification of soft tissues within the body such as the muscle and ligaments. This inappropriate formation of bone is highly prevalent in those affected by blast injuries. Here, we developed a simplified...

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Detalles Bibliográficos
Autores principales: Logan, Niall J., Camman, Marie, Williams, Greg, Higgins, Claire A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218666/
https://www.ncbi.nlm.nih.gov/pubmed/30219480
http://dx.doi.org/10.1016/j.bone.2018.09.008
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author Logan, Niall J.
Camman, Marie
Williams, Greg
Higgins, Claire A.
author_facet Logan, Niall J.
Camman, Marie
Williams, Greg
Higgins, Claire A.
author_sort Logan, Niall J.
collection PubMed
description Trauma-induced heterotopic ossification is an intriguing phenomenon involving the inappropriate ossification of soft tissues within the body such as the muscle and ligaments. This inappropriate formation of bone is highly prevalent in those affected by blast injuries. Here, we developed a simplified cell culture model to evaluate the molecular events involved in heterotopic ossification onset that arise from the shock wave component of the disease. We exposed three subtypes of human mesenchymal cells in vitro to a single, high-energy shock wave and observed increased transcription in the osteogenic master regulators, Runx2 and Dlx5, and significantly accelerated cell mineralisation. Reduced representation bisulfite sequencing revealed that the shock wave altered methylation of gene promoters, leading to opposing changes in gene expression. Using a drug to target ITGAV, whose expression was perturbed by the shock wave, we found that we could abrogate the deposition of mineral in our model. These findings show how new therapeutics for the treatment of heterotopic ossification can be identified using cell culture models.
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spelling pubmed-62186662018-12-01 Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model Logan, Niall J. Camman, Marie Williams, Greg Higgins, Claire A. Bone Article Trauma-induced heterotopic ossification is an intriguing phenomenon involving the inappropriate ossification of soft tissues within the body such as the muscle and ligaments. This inappropriate formation of bone is highly prevalent in those affected by blast injuries. Here, we developed a simplified cell culture model to evaluate the molecular events involved in heterotopic ossification onset that arise from the shock wave component of the disease. We exposed three subtypes of human mesenchymal cells in vitro to a single, high-energy shock wave and observed increased transcription in the osteogenic master regulators, Runx2 and Dlx5, and significantly accelerated cell mineralisation. Reduced representation bisulfite sequencing revealed that the shock wave altered methylation of gene promoters, leading to opposing changes in gene expression. Using a drug to target ITGAV, whose expression was perturbed by the shock wave, we found that we could abrogate the deposition of mineral in our model. These findings show how new therapeutics for the treatment of heterotopic ossification can be identified using cell culture models. Elsevier Science 2018-12 /pmc/articles/PMC6218666/ /pubmed/30219480 http://dx.doi.org/10.1016/j.bone.2018.09.008 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Logan, Niall J.
Camman, Marie
Williams, Greg
Higgins, Claire A.
Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model
title Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model
title_full Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model
title_fullStr Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model
title_full_unstemmed Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model
title_short Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model
title_sort demethylation of itgav accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218666/
https://www.ncbi.nlm.nih.gov/pubmed/30219480
http://dx.doi.org/10.1016/j.bone.2018.09.008
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