Demethylation of ITGAV Accelerates Osteogenic Differentiation in a Blast-Induced Heterotopic Ossification In Vitro Cell Culture Model

    December 2018 in “ Bone
    Niall Logan, Marie Camman, Greg Williams, Claire A. Higgins
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    TLDR Removing a methyl group from the ITGAV gene speeds up bone formation in a specific type of bone disease model.
    The document from December 2018 presents a study on the molecular mechanisms of heterotopic ossification (HO), particularly following blast injuries. The researchers used an in vitro cell culture model with human mesenchymal cells and found that a single high-energy shock wave led to increased transcription of osteogenic master regulators and accelerated cell mineralization. They discovered that the shock wave caused demethylation of gene promoters, notably the ITGAV gene, which resulted in increased transcription and osteogenic differentiation. The study showed that the drug cilengitide, an ITGAV inhibitor, could prevent mineral deposition, suggesting a potential therapeutic approach for HO. The study involved RT-qPCR validation with N=4 samples and a cilengitide concentration viability/proliferation test with n=4 for BM-MSCs and n=6 for mineral deposition quantification. The findings suggest that DNA methylation changes play a significant role in osteogenic differentiation and that DP cells can be used as a model to study HO and identify therapeutics.
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