Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model
File(s)
Published version
Supporting information
Author(s)
Logan, Niall
Camman, Marie
Williams, Greg
Higgins, Claire
Type
Journal Article
Abstract
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.
Date Issued
2018-12-01
Date Acceptance
2018-09-12
Citation
BONE, 2018, 117, pp.149-160
ISSN
8756-3282
Publisher
Elsevier
Start Page
149
End Page
160
Journal / Book Title
BONE
Volume
117
Copyright Statement
© 2018 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/BY/4.0/)
(http://creativecommons.org/licenses/BY/4.0/)
Sponsor
Medical Research Council (MRC)
Grant Number
MR/M01858X/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Epigenetic DNA methylation
Heterotopic ossification
In vitro model
Blast overpressure exposure
Ossification
MESENCHYMAL STEM-CELLS
TRAUMATIC BRAIN-INJURY
FOLLICLE DERMAL CELLS
SPINAL-CORD-INJURY
RISK-FACTORS
BONE-FORMATION
ADIPOGENIC DIFFERENTIATION
OSTEOBLAST DIFFERENTIATION
PAPILLA CELLS
STROMAL CELLS
11 Medical And Health Sciences
06 Biological Sciences
09 Engineering
Publication Status
Published
Date Publish Online
2018-09-13