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

Logan, Niall; Camman, Marie; Williams, Greg

doi:10.1016/j.bone.2018.09.008

Cited by 14 publications

(32 citation statements)

References 72 publications

(87 reference statements)

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“…It has been reported that activation of ITGA5 induced both IGF2 and IGFBP2 expressions via FAK, ERK1/2, and PI3K signaling, which resulted in osteogenic differentiation in hMSCs [ 53 ]. In another study, cilengitide (a cyclic RGD pentapeptide) is an ITGAV inhibitor [ 54 ] that can abolish ossification in BM-MSCs [ 55 ]. The interaction between osteopontin and integrin αv/β1 induced osteogenesis and inhibited adipogenesis in MSCs [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

et al. 2020

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Background Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into three lineages. They are suitable sources for cell-based therapy and regenerative medicine applications. This study aims to evaluate the hub genes and key pathways of differentially expressed genes (DEGs) related to osteogenesis by bioinformatics analysis in three different days. The DEGs were derived from the three different days compared with day 0. Results Gene expression profiles of GSE37558 were obtained from the Gene Expression Omnibus (GEO) database. A total of 4076 DEGs were acquired on days 8, 12, and 25. Gene ontology (GO) enrichment analysis showed that the non-canonical Wnt signaling pathway and lipopolysaccharide (LPS)-mediated signaling pathway were commonly upregulated DEGs for all 3 days. KEGG pathway analysis indicated that the PI3K-Akt and focal adhesion were also commonly upregulated DEGs for all 3 days. Ten hub genes were identified by CytoHubba on days 8, 12, and 25. Then, we focused on the association of these hub genes with the Wnt pathways that had been enriched from the protein-protein interaction (PPI) by the Cytoscape plugin MCODE. Conclusions These findings suggested further insights into the roles of the PI3K/AKT and Wnt pathways and their association with osteogenesis. In addition, the stem cell microenvironment via growth factors, extracellular matrix (ECM), IGF1, IGF2, LPS, and Wnt most likely affect osteogenesis by PI3K/AKT.

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Section: Discussionmentioning

confidence: 99%

Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

et al. 2020

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“…Integrin subunit alpha V (ITGAV), a member of the integrin family, has been found to be associated with cell differentiation and metastasis and can serve as a prognostic biomarker for a variety of cancers [29][30][31]. In our study, we found that ITGAV mRNA expression was significantly upregulated in CCA and that upregulated expression was associated with better prognosis in CCA patients through bioinformatics analysis.…”

Section: Discussionmentioning

confidence: 61%

Bioinformatics combined with quantitative proteomics analyses and identification of potential biomarkers in cholangiocarcinoma

Gao

et al. 2020

Cancer Cell Int

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Background: Cholangiocarcinoma (CCA) is an invasive malignancy arising from biliary epithelial cells; it is the most common primary tumour of the bile tract and has a poor prognosis. The aim of this study was to screen prognostic biomarkers for CCA by integrated multiomics analysis. Methods: The GSE32225 dataset was derived from the Gene Expression Omnibus (GEO) database and comprehensively analysed by using R software and The Cancer Genome Atlas (TCGA) database to obtain the differentially expressed RNAs (DERNAs) associated with CCA prognosis. Quantitative isobaric tags for relative and absolute quantification (iTRAQ) proteomics was used to screen differentially expressed proteins (DEPs) between CCA and nontumour tissues. Through integrated analysis of DERNA and DEP data, we obtained candidate proteins APOF, ITGAV and CASK, and immunohistochemistry was used to detect the expression of these proteins in CCA. The relationship between CASK expression and CCA prognosis was further analysed. Results: Through bioinformatics analysis, 875 DERNAs were identified, of which 10 were associated with the prognosis of the CCA patients. A total of 487 DEPs were obtained by using the iTRAQ technique. Comprehensive analysis of multiomics data showed that CASK, ITGAV and APOF expression at both the mRNA and protein levels were different in CCA compared with nontumour tissues. CASK was found to be expressed in the cytoplasm and nucleus of CCA cells in 38 (45%) of 84 patients with CCA. Our results suggested that patients with positive CASK expression had significantly better overall survival (OS) and recurrence-free survival (RFS) than those with negative CASK expression. Univariate and multivariate analyses demonstrated that negative expression of CASK was a significantly independent risk factor for OS and RFS in CCA patients. Conclusions: CASK may be a tumour suppressor; its low expression is an independent risk factor for a poor prognosis in CCA patients, and so it could be used as a clinically valuable prognostic marker.

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“…Previous work shows that DP cells, but not PFi, will readily differentiate down an osteogenic lineage in vitro [13], however it is not known if this is due to baseline differences in the epigenetic landscape between each cell type. To ascertain the baseline landscape, and determine if DP are pre-sensitised to differentiate down an osteogenic lineage in vitro, we assessed both the chromatin accessibility and transcriptional profiles of each cell type in GM, ATAC-seq and RNA-seq libraries were generated from DP and PFi cells grown in GM, with DNA and RNA isolated hours after cell seeding.…”

Section: Pfi and Dp Cells Share Similar Chromatin Organisation In Gm Conditionsmentioning

confidence: 95%

“…Lineage tracing studies have revealed that a fibroblast subtype found in the hair follicle, dermal papilla (DP) fibroblasts, share a common developmental progenitor with an interfollicular subtype, papillary fibroblasts (PFi) [9]. Despite arising from the same developmental progenitor [9], DP and PFi have distinct identities both in vivo and in vitro; DP cells can differentiate down osteogenic [10,11] and adipogenic [11,12] linages in vitro, while PFi lack this differentiation capacity [13]. DP and PFi also differ in their response to mechanical stimuli, and we previously demonstrated that mechanical stimulation of cells in culture (in the form of a single 165 kPa shock wave (SW) in air) in combination with osteogenic media (OM), resulted in enhanced and accelerated osteogenic differentiation of DP, whereas PFi were unresponsive to this stimuli [13].…”

Section: Introductionmentioning

confidence: 99%

“…Despite arising from the same developmental progenitor [9], DP and PFi have distinct identities both in vivo and in vitro; DP cells can differentiate down osteogenic [10,11] and adipogenic [11,12] linages in vitro, while PFi lack this differentiation capacity [13]. DP and PFi also differ in their response to mechanical stimuli, and we previously demonstrated that mechanical stimulation of cells in culture (in the form of a single 165 kPa shock wave (SW) in air) in combination with osteogenic media (OM), resulted in enhanced and accelerated osteogenic differentiation of DP, whereas PFi were unresponsive to this stimuli [13]. It is important to note that the SW alone could not promote ossification of DP, but rather it acted in a synergistic manner with OM, accelerating and enhancing mineral deposition in follicular derived DP cells [13].…”

Section: Introductionmentioning

confidence: 99%

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Chromatin accessibility profiling reveals that human fibroblasts respond to mechanical stimulation in a cell specific manner

Logan¹,

Pantelireis²,

Camman³

et al. 2021

Preprint

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Background: Fibroblasts in the skin are highly heterogeneous, both in vivo and in vitro. One intriguing difference between follicular and interfollicular fibroblasts in vitro is their ability to differentiate in response to osteogenic media, or mechanical stimulation. In this study, we asked whether differences in the ability to respond to differentiation stimuli are due to baseline differences in chromatin accessibility. Results: We performed chromatin accessibility and transcriptional profiling of two fibroblast subtypes found in human skin, which arise from a common progenitor during development yet display distinct characteristics in adult tissue and in vitro. We found that when cells were grown in regular growth media (GM) in culture they had unique chromatin accessibility profiles, however, these profiles control similar functional networks. When we introduced a chemical perturbation and grew cells in osteogenic media (OM) to promote differentiation, we observed a divergence not only in the accessible chromatin signatures but also in the functional networks controlled by these signatures. The biggest divergence was observed when we applied two perturbations to cells; growth in OM combined with mechanical stimulation in the form of a shock wave (OMSW). Here, in one of the fibroblast subtypes we found a number of uniquely accessible promoters which controlled osteogenic interaction networks associated with bone and differentiation functions. This fibroblast subtype also readily differentiates into bone in OMSW conditions, while the other fibroblast subtype under analysis lacks differentiation capability in vitro. Conclusions: Using ATAC-seq and RNA-seq we found that a combination of two stimuli could result significant and specific changes in chromatin accessibility associated with osteogenic differentiation, but only within the fibroblast sub-type capable of osteogenic differentiation. Our results suggest that these two stimuli elicit this cell specific response by modifying chromatin accessibility of osteogenic related gene promoters.

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

Cited by 14 publications

References 72 publications

Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

Bioinformatics combined with quantitative proteomics analyses and identification of potential biomarkers in cholangiocarcinoma

Chromatin accessibility profiling reveals that human fibroblasts respond to mechanical stimulation in a cell specific manner

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