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48-h stretched human periodontal ligament cells

ABSTRACT: Human periodontal ligament (HPDL) is continuously exposed to mechanical stress in vivo. In this study, in utilizing DNA chips, we analyzed the influences of mechanical stress on the gene expression profile of HPDL cells in vitro. HPDL cells were obtained from extracted first premolars of individuals undergoing tooth extraction for orthodontic treatment. Then, HPDL cells were applied to a stretch apparatus. They were constantly stretched and relaxed at 0.5 Hz for 48hr with 110％ force elongation. After the application of the cyclic tension force, total RNA was extracted. Then, in utilizing the DNA chips (Human Oligo 30K DNA Chip containing almost all human genes in the genome). We analyzed the differences of gene expression between the stretched and the non-stretched control HPDL cells The DNA chip analysis identified 17 up-regulated genes that showed at least 2-fold difference in their relative intensities between the stretched and the control. This result included the genes for the glutamate receptor binding protein: HOMER1, for the growth factor receptor: CNTFR, for the ECM remodeling protein: MMP15, for the protein interacting with calcineurin A: DSCR1, for the cytoskeletal protein: LRRFIP1, for the glutamate receptor: GRIN3A and some novel genes. On the basis of these data, we suggest that mechanical stress, in other words in vivo occlusal force, may affect the functions of HPDL cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE19118 | GEO | 2009/11/21

SECONDARY ACCESSION(S): PRJNA120471

REPOSITORIES: GEO

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48-h stretched human periodontal ligament cells

Project description:Human periodontal ligament (HPDL) is continuously exposed to mechanical stress in vivo. In this study, in utilizing DNA chips, we analyzed the influences of mechanical stress on the gene expression profile of HPDL cells in vitro. HPDL cells were obtained from extracted first premolars of individuals undergoing tooth extraction for orthodontic treatment. Then, HPDL cells were applied to a stretch apparatus. They were constantly stretched and relaxed at 0.5 Hz for 48hr with 110ï¼ force elongation. After the application of the cyclic tension force, total RNA was extracted. Then, in utilizing the DNA chips (Human Oligo 30K DNA Chip containing almost all human genes in the genome). We analyzed the differences of gene expression between the stretched and the non-stretched control HPDL cells The DNA chip analysis identified 17 up-regulated genes that showed at least 2-fold difference in their relative intensities between the stretched and the control. This result included the genes for the glutamate receptor binding protein: HOMER1, for the growth factor receptor: CNTFR, for the ECM remodeling protein: MMP15, for the protein interacting with calcineurin A: DSCR1, for the cytoskeletal protein: LRRFIP1, for the glutamate receptor: GRIN3A and some novel genes. On the basis of these data, we suggest that mechanical stress, in other words in vivo occlusal force, may affect the functions of HPDL cells Gene expression profiles were constructed using Human Oligo DNA Chip 30K (Hitachi software engineering) in human periodontal ligament cells (The 48-h stretched and the 48-h non-stretched, control).

2010-06-19 | E-GEOD-19118 | biostudies-arrayexpress

Expression profiling of mechanical stretched interfollicular epidermal stem cells (IFESCs)

Project description:The renewing human epidermis constantly senses and adapts to a wide range of mechanical cues that are ubiquitous throughout life. The mechanisms of how mechanical forces are responded by interfollicular epidermal stem cells (IFESCs) and are transmitted directly into nucleus to modify gene expression remain incompletely defined. In vitro, human IFESCs were cultured on the collagen I coated silicon rubber membrane and then subjected to the mechanical stretched. Cyclic mechanical tension at 0.5 Hz sinusoidal curve at 10% elongation was applied using an FX-5000T™ Flexercell® Tension Plus™ unit (Flexcell International Corporation). In mechanical unloading groups, cells were cultured on the same plates in the same incubator with the mechanical stretched groups but not subjected to stretch. Combining genome-wide microarray and functional analyses, we made transcriptome analysis of samples from the mechanical unstretched or stretched isolated human IFESCs.

2018-07-26 | GSE71391 | GEO

Expression data for C. elegans blunt force trauma

Project description:C. elegans exhibit an age-dependent mechanical stress response to blunt force injury. Stress responses are often defined in part by an elicited cellular transcriptional response. We find in C. elegans that mechanical stress by blunt trauma induces a distinct and age-dependent transcriptional program.

2020-04-09 | GSE148325 | GEO

Identification of genes regulated by mechanical tension in Xenopus laevis explants by transcriptome comparison

Project description:During gastrulation and neurulation, the chordamesoderm and overlying neuroectoderm of vertebrate embryos converge under the control of a specific genetic programme to the dorsal midline, simultaneously extending along it. However, whether mechanical tensions resulting from these morphogenetic movements play a role in long-range feedback signalling that in turn regulates gene expression in the chordamesoderm and neuroectoderm is unclear. In the present work, by using a model of artificially stretched explants of Xenopus midgastrula embryos and full-transcriptome sequencing, we identified genes with altered expression in response to external mechanical stretching. Importantly, mechanically activated genes appeared to be expressed during normal development in the trunk, i.e., in the stretched region only. By contrast, genes inhibited by mechanical stretching were normally expressed in the anterior neuroectoderm, where mechanical stress is low. These results indicate that mechanical tensions may play a role of a long-range signalling factor that regulates patterning of the embryo, serving as a link coupling morphogenesis and cell differentiation.

2024-01-31 | GSE246027 | GEO

Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation

Project description:<p>Mechanical force is critical for the development and remodeling of bone. Here we report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine (ADMA) via regulating the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 (Ddah1) expression in osteoblasts. The presence of -394 4N del/ins polymorphism of Ddah1 and higher serum ADMA concentration are negatively associated with bone mineral density. Global or osteoblast-specific deletion of Ddah1 leads to increased ADMA level but reduced bone formation. Further molecular study unveils that mechanical stimulation enhances TAZ/SMAD4-induced Ddah1 transcription. Deletion of Ddah1 in osteoblast-lineage cells fails to respond to mechanical stimulus-associated bone formation. Taken together, the study reveals mechanical force is capable of down-regulating ADMA to enhance bone formation.</p>

2021-11-23 | MTBLS3725 | MetaboLights

Regulation of the transcriptional response to mechanical trauma by vhp-1

Project description:Mechanical stress by blunt force trauma elicits a distinct and reproducible transcriptional response in C. elegans. Vhp-1, a MAPK phosphatase, regulates a significant portion of these stress-inducible transcripts.

2020-04-09 | GSE148337 | GEO

Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model [RNA-Seq]

Project description:Hypertrophic scars arise from dysregulated wound healing under prolonged mechanical tension, causing disfiguring fibrosis. However, limited preclinical models replicate key features of human tension-induced scarring. We developed an innovative murine model utilizing suture anchoring to impose persistent transverse-axial stretch across healing incisions, mimicking excessive wound tension that leads to hypertrophy clinically. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage while leaving wound edges on the lower back relaxed. This localized anchoring restrained wound contraction, maintaining high tension throughout remodeling analogous to scars widening under stress. Stretched upper wounds developed profound fibrotic changes compared to relaxed controls. Scars induced by suture-anchored tension displayed macroscopic hypertrophy, hardness, erythema, and pruritis up to 3 months. Histologically, scars induced by suture-anchored tension were hypercellular, hypervascular, hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. MRNA sequencing revealed the fibrogenic signature in suture-anchored tension induced hypertrophic scars, which exhibited transcriptional overlap with mechanically-stretched scars, human hypertrophic and keloid scars.

2023-09-28 | GSE243949 | GEO

Mechanical stress induced protein precipitation method for drug target screening

Project description:The process of protein precipitation can be used to decipher the interaction of ligand and protein. For example, the classic Thermal Proteome Profiling (TPP) method uses heating as the driving force for protein precipitation, to discover the drug target protein. Under heating or other denature forces, the target protein that binds with the drug compound will be more resistant to precipitation than the free protein. Similar to thermal stress, mechanical stress can also induce protein precipitation. Upon mechanical stress, protein will gradually precipitate along with protein conformational changes, which can be exploited for the study of the ligand-protein interaction. Herein, we proposed a Mechanical Stress Induced Protein Precipitation (MSIPP) method for drug target deconvolution. Its streamlined workflow allows in situ sample preparation on the surface of microparticles, from protein precipitation to digestion. The mechanical stress was generated by vortexing the slurry of protein solution and microparticle materials. The mechanical stress induced protein precipitate was captured by the microparticles, which guarantees the MSIPP method to be scalable and user-friendly. The MSIPP method was successfully applied to four drug compounds, Methotrexate, Raltitrexed, SHP099, Geldanamycin and a pan-inhibitor of protein kinases, Staurosporine. Besides, DHFR was demonstrated to be a target of Raltitrexed, which has not been revealed by any other modification-free drug target discovery method yet. Thus, MSIPP is a complementary method to other drug target screening methods.

2022-06-10 | PXD025528 | JPOST Repository

EZH2 Reduction Is an Essential Mechanoresponse for the Maintenance of Super-enhancer Polarization

Project description:Despite the ubiquitous mechanical cues at both spatial and temporal dimensions, cell identities and functions are largely immune to the everchanging mechanical stimuli. To understand the molecular basis of this epigenetic stability, we interrogated compressive force elicited transcriptomic changes in mesenchymal stem cells purified from human periodontal ligament (PDLSCs), and identified H3K27me3 and E2F signatures populated within up- and weakly down-regulated genes respectively. Consistently, expressions of several E2F family transcription factors and EZH2, as core methyltransferase for H3K27me3, decreased in response to mechanical stress, which were attributed to force induced redistribution of RB from nucleoplasm to lamina. Importantly, although epigenomic analysis on H3K27me3 landscape only demonstrated correlating changes at one group of mechanoresponsive genes, we observed a genome-wide destabilization of super-enhancers along with aberrant EZH2 retention. These super-enhancers were tightly bounded by H3K27me3 domain on one side and exhibited attenuating H3K27ac deposition and flattening H3K27ac peaks after force exposure, analogous to increased H3K27ac entropy or decreased H3K27ac polarization. Interference of force induced EZH2 reduction could drive nuclear actin filaments dependent collision between EZH2 and super-enhancers and functionally compromise the multipotency of PDLSC following mechanical stress. These findings together unveil a specific contribution of EZH2 reduction for maintenance of super-enhancer stability and cell identity in mechanoresponse.

2020-09-23 | GSE109166 | GEO

EZH2 Reduction Is an Essential Mechanoresponse for the Maintenance of Super-enhancer Polarization

2020-09-23 | GSE109167 | GEO

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