Pulsed electromagnetic fields increase osteogenetic commitment of MSCs via the mTOR pathway in TNF-α mediated inflammatory conditions: an in-vitro study

Ferroni, Letizia; Gardin, Chiara; Dolkart, Oleg; Salai, Moshe; Barak, Shlomo; Piattelli, Adriano; Amir-Barak, Hadar; Zavan, Barbara

doi:10.1038/s41598-018-23499-9

Cited by 49 publications

(37 citation statements)

References 38 publications

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“…Previous studies have found that integrin signaling pathway, mTOR signaling pathway, Wnt / β-catenin signaling pathway, Hippo pathway, and others, play important roles in traction osteogenesis. Some studies have found that Smad pathway, mitogen-activated protein kinase (MAPKs) pathway, etc., are also activated to varying degrees in osteotomy osteogenesis [35][36][37][38]. In our study, we found that ECM-receptor interaction, focal adhesion, Hippo signaling pathway-multiple species, PI3K-Akt signaling pathway, Wnt signaling pathway, Hippo signaling pathway, and other pathways show obvious trends of up-regulation in traction osteogenesis, thus indicating that these pathways may indeed be important in distraction osteogenesis.…”

Section: Discussionsupporting

confidence: 55%

Studies on trans-sutural distraction osteogenesis-related genes based on transcriptome sequencing

Wang

Xue

Tong

et al. 2020

Preprint

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Trans-sutural distraction osteogenesis (TSDO) is an important approach to improve mid-face hypoplasia. In recent years, many studies have been carried out on physical mechanisms of TSDO; however, it’s specific cytological and molecular mechanisms are still unclear. In this study, we performed transcriptome sequencing analysis in Sprague Dawley rats at 1 and 2 weeks after suture osteogenesis and compared RNA expression levels between experimental and control groups. At one week, enrichment pathways were mainly up-regulated in muscle- and bone-related pathways. By contrast, pathways of the immune system showed a state of inhibition and down-regulation, especially for B cells; the main immune pathways showed significant down-regulation. However, two weeks later, the experimental group showed positive up-regulation of the pathways related to DNA synthesis and replication, cell cycle, and chromosome replication. At the same time, the immune pathways that were down-regulated in the first week were up-regulated in the second week. In other words, the up-regulated muscle- and bone-related pathways show opposite trends. The expression of bone- and myogenesis-related transcriptome was up-regulated and the immune-related pathways were down-regulated in the experimental group at 1 week. At 2 weeks, the pathways related to bone- and muscle were down-regulated, while those related to cell cycle regulation and DNA replication were up-regulated. These results suggest that musculoskeletal-related molecules may play an important role during suture osteogenesis at 1 week, and immune regulation may be involved in this process; however, at 2 weeks, molecules related to cell proliferation and replication may be a major role.

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Section: Discussionsupporting

confidence: 55%

Studies on trans-sutural distraction osteogenesis-related genes based on transcriptome sequencing

Wang

Xue

Tong

et al. 2020

Preprint

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“…Once isolated, hADSCs were induced to osteogenic differentiation and contextually exposed to HBO, HB or HO daily for 60 min, with the aim to replicate the duration of treatment received by hyperbaric therapy patients [3]. Each treatment was carried out for 21 days, which is generally considered an appropriate time period for in vitro evaluating the osteogenic differentiation properties of hADSCs [30].…”

Section: Discussionmentioning

confidence: 99%

Hyperbaric Oxygen Therapy Improves the Osteogenic and Vasculogenic Properties of Mesenchymal Stem Cells in the Presence of Inflammation In Vitro

Gardin

Bosco

Ferroni

et al. 2020

IJMS

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Hyperbaric oxygen (HBO) therapy has been reported to be beneficial for treating many conditions of inflammation-associated bone loss. The aim of this work was to in vitro investigate the effect of HBO in the course of osteogenesis of human Mesenchymal Stem Cells (MSCs) grown in a simulated pro-inflammatory environment. Cells were cultured with osteogenic differentiation factors in the presence or not of the pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α), and simultaneously exposed daily for 60 min, and up to 21 days, at 2,4 atmosphere absolute (ATA) and 100% O2. To elucidate osteogenic differentiation-dependent effects, cells were additionally pre-committed prior to treatments. Cell metabolic activity was evaluated by means of the MTT assay and DNA content quantification, whereas osteogenic and vasculogenic differentiation was assessed by quantification of extracellular calcium deposition and gene expression analysis. Metabolic activity and osteogenic properties of cells did not differ between HBO, high pressure (HB) alone, or high oxygen (HO) alone and control if cells were pre-differentiated to the osteogenic lineage. In contrast, when treatments started contextually to the osteogenic differentiation of the cells, a significant reduction in cell metabolic activity first, and in mineral deposition at later time points, were observed in the HBO-treated group. Interestingly, TNF-α supplementation determined a significant improvement in the osteogenic capacity of cells subjected to HBO, which was not observed in TNF-α-treated cells exposed to HB or HO alone. This study suggests that exposure of osteogenic-differentiating MSCs to HBO under in vitro simulated inflammatory conditions enhances differentiation towards the osteogenic phenotype, providing evidence of the potential application of HBO in all those processes requiring bone regeneration.

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“…In our samples we found a great quantity of ROS and high gene expression levels of mitochondrial genes related to ROS production, confirming the abnormal presences of this marker in the peri-implantitic tissue. Moreover, in recent years researchers highlighted its role as signaling molecules [17][18][19][20] impacting MSC differentiation. Evidence supports the strong relation with impaired skeletal integrity: increased levels of intracellular ROS induce the MSC potential in osteogenic differentiation [21][22][23][24][25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Presence of ROS in Inflammatory Environment of Peri-Implantitis Tissue: In Vitro and In Vivo Human Evidence

Mijiritsky

Ferroni

Gardin

et al. 2019

JCM

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Analyses of composition, distribution of cellular and extracellular matrix components, and molecular analysis of mitochondria related genes of bone loss in the presence of inflammatory environment in humans was the aim of the present project. As a human model we chose peri-implantitis. Morphological analyses were performed by means classical histological, immunohistochemical, and SEM (scanning electron miscroscopy) test. Gene expression analysis was performed to evaluate epithelium maturation, collagen fiber production, and genes related to mitochondrial activity. It was found that a well-defined keratinocyte epithelium was present on the top of all specimens; a distinct basal lamina was present, as well as desmosomes and autophagic processes related to the maturation of keratinocytes. Under this epithelium, a full inflammatory cell infiltrate was present for about 60% of the represented by plasma cells. Collagen type I fibers were present mainly in the form of fragmented cord tissue without cells. A different distribution of blood vessels was also present from the apical to the most coronal portion of the specimens. High levels of genes related to oxidative stress were present, as well as the activation of genes related to the loss of ability of osteogenic commitment of Mesenchymal stem cells into osteoblasts. Our study suggests that peri-implantitis lesions exhibit a well defined biological organization not only in terms of inflammatory cells but also on vessel and extracellular matrix components even if no difference in the epithelium is evident, and that the presence of reactive oxygen species (ROS) related to the inflammatory environment influences the correct commitment of Mesenchymal stem cells.

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Pulsed electromagnetic fields increase osteogenetic commitment of MSCs via the mTOR pathway in TNF-α mediated inflammatory conditions: an in-vitro study

Cited by 49 publications

References 38 publications

Studies on trans-sutural distraction osteogenesis-related genes based on transcriptome sequencing

Studies on trans-sutural distraction osteogenesis-related genes based on transcriptome sequencing

Hyperbaric Oxygen Therapy Improves the Osteogenic and Vasculogenic Properties of Mesenchymal Stem Cells in the Presence of Inflammation In Vitro

Presence of ROS in Inflammatory Environment of Peri-Implantitis Tissue: In Vitro and In Vivo Human Evidence

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