Biomechanical strain-induced modulation of proliferation coincides with an ERK1/2-independent nuclear YAP localization

Hülter-Hassler, Diana; Wein, Martin; Schulz, Simon; Proksch, Susanne; Steinberg, Thorsten; Jung, Britta A.; Tomakidi, Pascal

doi:10.1016/j.yexcr.2017.10.006

Cited by 16 publications

(9 citation statements)

References 33 publications

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“…Furthermore, they demonstrated that knockdown of YAP induced the apoptosis and inhibited the proliferation of human periodontal ligament stem cells (h-PDLSCs) through crosstalk between Erk and Bcl-2 signaling pathway, suggesting that YAP signaling pathway participated in regulating biological behaviors of h-PDLSCs [ 26 ]. Diana Huelter-Hassler also found that the activated YAP might contribute to the enhanced proliferation of HPDLCs during orthodontic tooth movement [ 27 , 28 ]. Importantly, it was reported that the mechanical stress increased the expression levels of osteogenesis-related genes ALP and type I collagen in HPDLCs, and the mechanical stimulation also influenced the maintenance of periodontal ligament and alveolar bone formation [ 3 ].…”

Section: Resultsmentioning

confidence: 99%

Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation

Yang

Wang

Chang

et al. 2018

BioMed Research International

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Periodontal remodeling and alveolar bone resorption and formation play essential roles during orthodontic tooth movement (OTM). In the process, human periodontal ligament cells (HPDLCs) sense and respond to orthodontic forces, contributing to the alveolar bone formation. However, the underlying mechanism in this process is not fully elucidated. In the present study, cyclic stress stimulus was applied on HPDLCs to mimic the orthodontic forces during OTM. Our results demonstrated that cyclic stretch promoted the osteogenic differentiation of HPDLCs. Moreover, our data suggested that yes-associated protein (YAP), the Hippo pathway effector, which also involved in mechanical signaling transduction, was activated as we found that the nuclear translocation of YAP was significantly increased in the cyclic stress treated HPDLCs. The mRNA expression of CTGF and CYR61, the target genes of YAP, was also remarkably increased. Furthermore, knockdown of YAP suppressed the cyclic stretch induced osteogenesis in HPDLCs, while overexpression of YAP in HPDLCs enhanced osteogenesis. We also noticed that YAP activities could be suppressed by the ROCK and nonmuscle myosin II inhibitors, Y-27632 and Blebbistatin. The inhibitors also significantly inhibited the cyclic stretch induced osteogenesis in HPDLCs. Finally, in the murine OTM model, our results revealed that YAP was upregulated and nuclearly translocated in the PDLCs at the tension side. In summary, our present study demonstrated that cytoskeleton remodeling induced activation of YAP signaling pathway was crucial for the cyclic stretch-induced osteogenesis of HPDLCs, which might play important roles during OTM.

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Section: Resultsmentioning

confidence: 99%

Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation

Yang

Wang

Chang

et al. 2018

BioMed Research International

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“…Recent research on YAP/TAZ has demonstrated that the inhibition of the expression and transcriptional activity of YAP/TAZ could significantly inhibit the growth and invasion in tumor cells, and induces tumor cells apoptosis [77–79]. Treating tumor cells with Verteporfin, a target drugs for YAP/TAZ, significantly reversed the malignant biological behavior of the tumor cells [80–83]. Therefore, YAP/TAZ may represent ideal targets for selective tumor therapy.…”

Section: Discussionmentioning

confidence: 99%

The role of YAP/TAZ activity in cancer metabolic reprogramming

et al. 2018

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In contrast to normal cells, which use the aerobic oxidation of glucose as their main energy production method, cancer cells prefer to use anaerobic glycolysis to maintain their growth and survival, even under normoxic conditions. Such tumor cell metabolic reprogramming is regulated by factors such as hypoxia and the tumor microenvironment. In addition, dysregulation of certain signaling pathways also contributes to cancer metabolic reprogramming. Among them, the Hippo signaling pathway is a highly conserved tumor suppressor pathway. The core oncosuppressive kinase cascade of Hippo pathway inhibits the nuclear transcriptional co-activators YAP and TAZ, which are the downstream effectors of Hippo pathway and oncogenic factors in many solid cancers. YAP/TAZ function as key nodes of multiple signaling pathways and play multiple regulatory roles in cancer cells. However, their roles in cancer metabolic reprograming are less clear. In the present review, we examine progress in research into the regulatory mechanisms of YAP/TAZ on glucose metabolism, fatty acid metabolism, mevalonate metabolism, and glutamine metabolism in cancer cells. Determining the roles of YAP/TAZ in tumor energy metabolism, particularly in relation to the tumor microenvironment, will provide new strategies and targets for the selective therapy of metabolism-related cancers.

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“…Howard et al, 1998;Kletsas et al, 2002;Konstantonis et al, 2014;Chen et al, 2015); 3) in vitro studies defining an "optimal" window to study the expression of specific genes or pathways (e.g. Basdra et al, 1996;Hao et al, 2009;Huelter-Hassler et al, 2017;Hülter-Hassler et al, 2017).…”

Section: Rationale For Force Parametersmentioning

confidence: 99%

Effect of Tension on Human Periodontal Ligament Cells: Systematic Review and Network Analysis

Sun

Ranković

Folwaczny

et al. 2021

Front. Bioeng. Biotechnol.

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Orthodontic tooth movement is based on the remodeling of tooth-surrounding tissues in response to mechanical stimuli. During this process, human periodontal ligament cells (hPDLCs) play a central role in mechanosensing and mechanotransduction. Various in vitro models have been introduced to investigate the effect of tension on hPDLCs. They provide a valuable body of knowledge on how tension influences relevant genes, proteins, and metabolites. However, no systematic review summarizing these findings has been conducted so far. Aim of this systematic review was to identify all related in vitro studies reporting tension application on hPDLCs and summarize their findings regarding force parameters, including magnitude, frequency and duration. Expression data of genes, proteins, and metabolites was extracted and summarized. Studies’ risk of bias was assessed using tailored risk of bias tools. Signaling pathways were identified by protein-protein interaction (PPI) networks using STRING and GeneAnalytics. According to our results, Flexcell Strain Unit® and other silicone-plate or elastic membrane-based apparatuses were mainly adopted. Frequencies of 0.1 and 0.5 Hz were predominantly applied for dynamic equibiaxial and uniaxial tension, respectively. Magnitudes of 10 and 12% were mostly employed for dynamic tension and 2.5% for static tension. The 10 most commonly investigated genes, proteins and metabolites identified, were mainly involved in osteogenesis, osteoclastogenesis or inflammation. Gene-set enrichment analysis and PPI networks gave deeper insight into the involved signaling pathways. This review represents a brief summary of the massive body of knowledge in this field, and will also provide suggestions for future researches on this topic.

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Biomechanical strain-induced modulation of proliferation coincides with an ERK1/2-independent nuclear YAP localization

Cited by 16 publications

References 33 publications

Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation

Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation

The role of YAP/TAZ activity in cancer metabolic reprogramming

Effect of Tension on Human Periodontal Ligament Cells: Systematic Review and Network Analysis

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