Changes in gene expression after mechanical loading with and without satellite cell.
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ABSTRACT:
PROVIDER: PRJNA745472 | ENA |
REPOSITORIES: ENA
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Project description:Skeletal muscle is a plastic tissue, adapting to different stimuli. Mechanical overload causes muscle hypertrophy and substantial changes in gene expression. We perform a time course analysis following synergistic ablation surgery to induce compensatory hypertrophy in the plantaris muscle in satellite cell depleted mice and wild-type mice. Microarray was used to determine the different expressed genes in skeletal muscle with or without satellite cell following mechanical overload.
2021-07-12 | GSE153542 | GEO
Project description:Muscle stem cells, or satellite cells, decline in number with age and may become senescent. Whether and how satellite cells contribute to muscle adaptation in the oldest-old is unclear. Using short-term mechanical overload in geriatric satellite cell replete and depleted mice (28 months of age) combined with single cell RNA-sequencing, we show: 1) subsets of geriatric satellite cells show signs of senescence as well as normal fate progression during overload, 2) satellite cells express markers that may contribute to the regulation of innervation, 3) the presence of satellite cells during overload globally enhances intercellular communication and causes upregulation of the cell surface receptor gene Cd74 in immune cells, 4) Mif, the primary ligand for CD74, is produced by fibrogenic cells and is more pronounced in the absence of satellite cells - perhaps to help normalize dysregulated fibrotic signaling, and 5) satellite cells drive fate directive transcript splicing that promotes the canonical macrophage response to hypertrophic loading. Our findings expose the behavior of satellite cells in response to mechanical loading in the oldest-old and reveal a satellite cell-macrophage-fibrogenic cell circuit in geriatric muscle that may promote extracellular matrix remodeling
2025-08-28 | GSE291156 | GEO
Project description:Skeletal integrity in humans and animals is maintained by daily mechanical loading. It has been widely accepted that osteocytes function as mechanosensors. Many biochemical signaling molecules are involved in the response of osteocytes to mechanical stimulation. The aim of this study was to identify genes involved in the translation of mechanical stimuli into bone formation. The four-point bending model was used to induce a single period of mechanical loading (comprising 300 cycles (2 Hz) using a peak magnitude of 60 N) on the right tibia, while the contra lateral left tibia served as control. Six hours after loading, the effects of mechanical loading on gene-expression were determined with microarray analysis. Protein expression of differentially regulated genes was evaluated with immunohistochemistry. Nine genes were found to exhibit a significant differential gene expression in LOAD compared to control. MEPE, Garnl1, V2R2B, and QFG TN1 olfactory receptor were up-regulated, and creatine kinase (muscle form), fibrinogen-B beta-polypeptide, monoamine oxidase A, troponin-C and kinesin light chain-C were down-regulated. Validation with real-time RT-PCR analysis confirmed the up regulation of MEPE and the down-regulation of creatine kinase (muscle form) and troponin-C in the loaded tibia. Immunohistochemistry showed that the increase of MEPE protein expression was already detectable six hours after mechanical loading. In conclusion, these genes probably play a role during translation of mechanical stimuli six hours after mechanical loading. The modulation of MEPE expression may indicate a connection between bone mineralization and bone formation after mechanical stimulation. Two groups: LOAD vs contralateral control and SHAM vs contralateral control (n=5/group)
2013-11-21 | E-GEOD-50707 | biostudies-arrayexpress
Project description:Skeletal integrity in humans and animals is maintained by daily mechanical loading. It has been widely accepted that osteocytes function as mechanosensors. Many biochemical signaling molecules are involved in the response of osteocytes to mechanical stimulation. The aim of this study was to identify genes involved in the translation of mechanical stimuli into bone formation. The four-point bending model was used to induce a single period of mechanical loading (comprising 300 cycles (2 Hz) using a peak magnitude of 60 N) on the right tibia, while the contra lateral left tibia served as control. Six hours after loading, the effects of mechanical loading on gene-expression were determined with microarray analysis. Protein expression of differentially regulated genes was evaluated with immunohistochemistry. Nine genes were found to exhibit a significant differential gene expression in LOAD compared to control. MEPE, Garnl1, V2R2B, and QFG TN1 olfactory receptor were up-regulated, and creatine kinase (muscle form), fibrinogen-B beta-polypeptide, monoamine oxidase A, troponin-C and kinesin light chain-C were down-regulated. Validation with real-time RT-PCR analysis confirmed the up regulation of MEPE and the down-regulation of creatine kinase (muscle form) and troponin-C in the loaded tibia. Immunohistochemistry showed that the increase of MEPE protein expression was already detectable six hours after mechanical loading. In conclusion, these genes probably play a role during translation of mechanical stimuli six hours after mechanical loading. The modulation of MEPE expression may indicate a connection between bone mineralization and bone formation after mechanical stimulation.
2013-11-21 | GSE50707 | GEO
Project description:The advent of high-throughput measurements of gene expression and bioinformatics analysis methods offers new ways to study gene expression patterns. The primary goal of this study was to determine the time sequence for gene expression in a bone subjected to mechanical loading, during key periods of the bone formation process, including expression of matrix-related genes, the appearance of active osteoblasts, and bone desensitization. A standard model for bone loading was employed in which the right forelimb was loaded axially for three minutes per day, while the left forearm served as a non-loaded, contralateral control. We evaluated loading-induced gene expression over a time course of 4 hours to 32 days after the first loading session. Six distinct, time-dependent patterns of gene expression were identified over the time course and categorized into three primary clusters: genes upregulated early in the time course, genes upregulated during matrix formation, and genes downregulated during matrix formation. Genes were then grouped based on function and/or signaling pathways. Many gene groups known to be important in loading-induced bone formation were identified within the clusters, including AP-1-related genes in the early response cluster, matrix-related genes in the upregulated gene clusters, and Wnt/?-catenin signaling pathway inhibitors in the downregulated gene clusters. Several novel gene groups were identified as well, including chemokine-related genes which were upregulated early but downregulated later in the time course, solute carrier genes which were both up- and downregulated, and muscle-related genes which were primarily downregulated. Time Course with 11 time points, each plus & minus mechanical stimulation with 5 replicates per experimental group (except 12d group which has 4 replicates). Daily mechanical loading was applied to the forearm (24 hours between loading sessions), and ulnae were sampled at indicated time points (4h, 12h, 1d, 2d, 4d, 6d, 8d, 12d, 16d, 24d, or 32d).
2010-06-12 | E-GEOD-22286 | biostudies-arrayexpress
Project description:Evidences indicate that mechanical loading plays an important role in osteoarthritis (OA) progression, while the specific pathological changes of the synovium under excessive mechanical loading are unclear. Results showed excessive mechanical loading caused pro-inflammatory of synovial macrophages, which has been confirmed to exists in OA. High Rapgef3 expression level was found in RNA sequencing of RAW246.7 subjected to 0.5Hz-20%-cyclic tensile strain. We verified this in the synovium of OA patients and DMM-OA mice. Interestingly, the Rapgef3 content of chondrocytes was very low. Primary chondrocytes treated with Rapgef3 alone did not show metabolic phenotype, but an OA phenotype appeared when treated with Rapgef3-stimulated macrophage culture supernatant. Mechanically, excessive mechanical loading activated p65-NF-κB pathway through Rapgef3, which promoted the inflammatory of macrophage, resulting in severe articular cartilage injury. Intra-articular Rapgef3 knockout reversed synovitis and cartilage degeneration, which might provide a therapeutic target for osteoarthritis.
2024-11-04 | GSE280230 | GEO
Project description:Satellite Cells Choreograph an Immune Cell-Fibrogenic Cell Circuit During Mechanical Loading in Geriatric Skeletal Muscle
| PRJNA1232112 | ENA
Project description:The mechano-responsiveness of osteocytes is critical for maintaining bone health, yet the molecular mechanisms underlying this process remain poorly understood. Here, we investigate the impact of mechanical loading on transcriptional and epigenetic remodeling in osteocytes. Using MLO-Y4 cells, we subjected osteocytes to mechanical loading and profiled their transcriptome and histone modifications. Our findings revealed significant transcriptional and epigenetic changes, with NRF2 emerging as a key regulator. We demonstrated that mechanical loading stabilizes NRF2 protein levels and promotes its nucleus translocation, leading to enhanced genomic binding of NRF2 and activation of its target genes. Further analysis confirmed cell type-specific functions of NRF2, with distinct binding profiles in osteocytes compared to astrocytes. These results highlight the pivotal role of NRF2 in the mechano-responsiveness of osteocytes. Unlike pharmacologic agents that stabilize NRF2, mechanical loading uniquely promoted NRF2 nucleus translocation and transcriptional activity. This underscores the irreplaceable role of mechanical stimuli, such as exercise, in promoting bone health. This study advances our understanding of osteocyte mechanotransduction and identifies potential therapeutic interventions for bone diseases.
2025-04-03 | GSE273537 | GEO
Project description:The mechano-responsiveness of osteocytes is critical for maintaining bone health, yet the molecular mechanisms underlying this process remain poorly understood. Here, we investigate the impact of mechanical loading on transcriptional and epigenetic remodeling in osteocytes. Using MLO-Y4 cells, we subjected osteocytes to mechanical loading and profiled their transcriptome and histone modifications. Our findings revealed significant transcriptional and epigenetic changes, with NRF2 emerging as a key regulator. We demonstrated that mechanical loading stabilizes NRF2 protein levels and promotes its nucleus translocation, leading to enhanced genomic binding of NRF2 and activation of its target genes. Further analysis confirmed cell type-specific functions of NRF2, with distinct binding profiles in osteocytes compared to astrocytes. These results highlight the pivotal role of NRF2 in the mechano-responsiveness of osteocytes. Unlike pharmacologic agents that stabilize NRF2, mechanical loading uniquely promoted NRF2 nucleus translocation and transcriptional activity. This underscores the irreplaceable role of mechanical stimuli, such as exercise, in promoting bone health. This study advances our understanding of osteocyte mechanotransduction and identifies potential therapeutic interventions for bone diseases.
2025-04-03 | GSE273535 | GEO
Project description:Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding). The presence of tissue niche-dependent physiological time cues has been proposed, allowing tissues the ability of circadian phase adjustment based on local signals. However, to date, such stimuli have remained elusive. Here we show that daily patterns of mechanical loading and associated osmotic challenge within physiological ranges reset circadian clock phase and amplitude in cartilage and intervertebral disc tissues in vivo and in tissue explant cultures. Hyperosmolarity (but not hypo-osmolarity) resets clocks in young and ageing skeletal tissues and induce genome-wide expression of rhythmic genes in cells. Mechanistically, RNAseq and biochemical analysis revealed the PLD2-mTORC2-AKT-GSK3β axis as a convergent pathway for both in vivo loading and hyperosmolarity-induced clock changes. These results reveal diurnal patterns of mechanical loading and consequent daily surges in osmolarity as a bona fide tissue niche-specific time cue to maintain skeletal circadian rhythms in sync.
2023-08-17 | E-MTAB-12877 | biostudies-arrayexpress