Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1227172 | ENA |
REPOSITORIES: ENA
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Project description:Muscle wasting and weakness are important clinical problems that limit mobility and independence, shortening health span and increasing physical disability risk. The molecular basis for this has not been fully determined. Klotho expression is downregulated in conditions associated with muscle wasting, including aging, chronic kidney disease, and myopathy. The objective of this study was to investigate a mechanistic role for Klotho in regulating muscle wasting and weakness. Body weight, lean mass, muscle mass, and myofiber caliber were reduced in Klotho-deficient mice. In the tibialis anterior muscle of Klotho null mice, type IIa myofibers were resistant to changes in size, and muscle composition differed with a higher concentration of type IIb fibers to the detriment of type IIx fibers. Glycolytic enzymatic activity also increased. Klotho-deficient mice showed impaired muscle contractility, with reduced twitch force, torque, and contraction-relaxation rates. RNA-sequencing revealed upregulation of synaptic and fetal sarcomeric genes, prompting us to examine muscle innervation. Klotho-deficiency led to neuromuscular junction remodeling, myofiber denervation, and functional motor unit loss. Loss of motor units correlated with absolute torque. Collectively, these findings reveal a novel mechanism through which Klotho-deficiency disrupts muscle synapses and motor unit connectivity, likely influences muscle wasting and weakness.
2025-09-03 | GSE302925 | GEO
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
Project description:This project mainly studies the effect of mechanical force on the protein expression pattern of MSCs.
2025-06-26 | PXD065487 |
Project description:The ability of the skin to expand in response to stretching has, for decades, been exploited in reconstructive surgery. Several studies have investigated the response of stretching epidermal cells in vitro. However, it remains unclear how mechanical forces affect epidermal stem cell behaviour in vivo. Here, we develop a mouse model in which the temporal consequences of the stretching the skin epidermis can be studied. Using a multidisciplinary approach that combines clonal analysis and mathematical modelling, we show that mechanical force induces skin expansion by promoting the renewal of epidermal stem cells. This occurs through a structured response in which cell fates are coordinated locally by stem cells that switch between states primed for renewal or differentiation. Transcriptional and chromatin profiling identifies the gene regulatory networks modulated by mechanical force. Using a combination of pharmacological inhibition and several conditional gene loss-of-function mouse mutants, we dissect the signalling pathways that control force-mediated tissue expansion.
2020-05-18 | GSE126734 | GEO
Project description:To assess the transcriptomic response to Klotho deficiency in the renal distal convolution (DC), we isolated DC cells from control and DC-specific Klotho KO mice using COPAS (Complex Object Parametric Analyzer and Sorter). Further comprehensive and unbiased RNA-seq identified altered transcripts associated with canonical MAPK pathway, as well as many novel targets of Klotho.
2023-12-15 | GSE247008 | GEO
Project description:Macrophages play a pivotal role in mechanical force-induced inflammatory bone remodeling. Yet, how macrophages perceive mechanical stimuli and thereby modulate biological behaviors remain elusive. The orthodontic tooth movement (OTM) model was established to access the role of Piezo1 in modulating macrophage response upon mechanical stimuli. The potential functions and molecule mechanisms of Piezo1 were explored by bone marrow-derived macrophages (BMDMs) using mechanical stretch system, western blotting, immunofluorescence, flow cytometry and RNA sequencing. We first found macrophage proliferative phenotype enhanced at the later stage of force application. The biological variation mediated by mechanical force could be suppressed by Piezo1 inhibition. Furthermore, Piezo1 activated PI3K-AKT signaling was closely associated with macrophage proliferation upon mechanical stimuli. Additionally, Ccnd1 was authenticated as a critical downstream factor of PI3K-AKT signaling and conditional ablation of Ccnd1 in macrophages inhibited macrophage proliferation in mechanical force-induced bone remodeling procedure.
2024-12-08 | GSE190470 | GEO
Project description:The ability of the skin to expand in response to stretching has, for decades, been exploited in reconstructive surgery. Several studies have investigated the response of stretching epidermal cells in vitro. However, it remains unclear how mechanical forces affect epidermal stem cell behaviour in vivo. Here, we develop a mouse model in which the temporal consequences of the stretching the skin epidermis can be studied. Using a multidisciplinary approach that combines clonal analysis and mathematical modelling, we show that mechanical force induces skin expansion by promoting the renewal of epidermal stem cells. This occurs through a structured response in which cell fates are coordinated locally by stem cells that switch between states primed for renewal or differentiation. Transcriptional and chromatin profiling identifies the gene regulatory networks modulated by mechanical force. Using a combination of pharmacological inhibition and several conditional gene loss-of-function mouse mutants, we dissect the signalling pathways that control force-mediated tissue expansion. We used microarray to molecularly profile basal cells isolated from the interfolliular epidermis during force-mediated tissue expansion and after 12-O-Tetradecanoylphorbol-13-acetate (TPA) tretment.
2020-05-18 | GSE126231 | GEO
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
Project description:To explore the effect of magnetic mechanical force mediated by magnetic nanoparticles in a gradient magnetic field environment on the repair phenotype of Schwann cells in injured sciatic nerves, we established a rat sciatic nerve crush injury model and locally injected magnetic nanoparticles under the epineurium at the distal end of the crush site.
2025-08-24 | GSE306137 | GEO