Mechanical Loading remodels transcriptional regulation in Osteocytes through Nucleus translocation of NRF2 [RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1142070 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30043707_1.fastq.gz | Fastqsanger.gz | |||
| SRR30043707_2.fastq.gz | Fastqsanger.gz | |||
| SRR30043708_1.fastq.gz | Fastqsanger.gz | |||
| SRR30043708_2.fastq.gz | Fastqsanger.gz | |||
| SRR30043709_1.fastq.gz | Fastqsanger.gz |
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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:Mechanical Loading remodels transcriptional regulation in Osteocytes through Nucleus translocation of NRF2 [ChIP-seq]
| PRJNA1142069 | ENA
Project description:Aim: To identify differentially expressed genes by mapping the response of human primary osteocytes in their native matrix to mechanical loading using RNA sequencing.
2023-01-30 | GSE220630 | 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:A previous study indicated that mechanical tensile strain of 2500 microstrain (με) at 0.5 Hz for 8 h promoted osteogenesis and corresponding mechanoresponsive microRNAs (miRs) were identified in osteoblasts. However, in osteocytes, it has not been identified which miRs respond to the mechanical strain, and it is not fully understood how the mechanoresponsive miRs regulate osteoblast differentiation. Mouse MLO-Y4 osteocytes were applied to the same mechanical tensile strain in vitro.MiR microarray and reverse transcription-quantitative polymerase chainreaction(RT-qPCR) assays were applied to select and validate differentially expressed miRs, and the target genes of these miRs were then predicted. In addition, the differentially expressed miRNAs in mechanically strained osteocytes in vitro were compared with those in treadmill exercise of the bone tissues .
2021-07-02 | GSE179199 | GEO
Project description:Mechanical loading influences osteocytes and further regulates osteoblast metabolism and osteogenic differentiation(miRNA Array)
| PRJNA742690 | ENA
Project description:Mapping the response of human osteocytes in native matrix to mechanical loading using RNA sequencing
| PRJNA910567 | ENA
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