Novel Role of Estrogen Receptor-α on Regulating Chondrocyte Phenotype and Response to Mechanical Loading
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ABSTRACT:
PROVIDER: PRJNA744755 | ENA |
REPOSITORIES: ENA
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Project description:Using bulk RNA-seq for chondrocytes isolated from preserved cartilage and damaged cartilage, 558 differentially expressed genes were identified. Given the shared genetic and biochemical environment of D-C and P-C located within the same knee, the differences in tissue integrity and resulting chondrocyte phenotype could in part be attributed to differences in the mechanical microenvironment; Through ingenuity pathway analysis and other molecular biology method, we identified ESR1 as a promosing up-stream regulator which could regulate chondrocyte phenotype and reponse to mechanical loading.
2023-07-07 | GSE179716 | 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:To investigate potential mechanisms for the synergism of L-BAIBA and mechanical loading on bone formation, RNA Seq was performed on osteocyte-enriched cortical bone from mice treated with L-BAIBA and sub-optimal mechanical loading (8.25N) for either long-term (2 weeks L-BAIBA and loading) or short-term (5 days L-BAIBA and a single bout of mechanical loading).
2023-02-01 | GSE214582 | GEO
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:Cell viability and global gene expression was anayzed from collagen 1 hydrogel scaffolds following 3 hours of cyclic mechanical loading and compared with non-loaded scaffolds. Experiment Overall Design: 6 samples are analyzed (2 sets in triplicate). The first set is the Loaded condition in which Collagen 1 hydrogels seeded with Human dermal fibroblasts underwent cyclic loading of 0.1Hz for 180 minutes at 37 degrees Celsius. The second set is the control Unloaded condition in which the Collagen 1 hydrogels seeded with Human dermal fibroblasts are incubated at 37 degrees Celsius with no loading.
2008-06-11 | E-GEOD-10125 | biostudies-arrayexpress
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
Project description:Hydrostatic pressure is one of the main mechanical stimuli cartilage cells are submitted to during joint loading. If moderate hydrostatic pressure is known to be beneficial to cartilage differentiation, excessive pressure, on the other hand, induces changes in cartilage similar to those observed in osteoarthritic cartilage. Therefore, the purpose of the experiment is to identify new target genes of high hydrostatic pressure in chondrocyte precursor cells.
2017-12-02 | E-MTAB-5326 | biostudies-arrayexpress
Project description:The objective of our study was to use a microarray to distinguish the molecular responses between woven and lamellar bone formation induced through mechanical loading. The micorarray identified numerous genes and pathways that were differentially regulated for woven, but not lamellar bone formation. Rat forelimb loading was completed in a single bout to induce the formation of woven bone (WBF loading) or lamellar bone (LBF loading). A set of normal (non-loaded) rats were used as controls. Microarrays were performed at three timepoints after loading: 1 hr, 1 day and 3 days.
2013-01-01 | E-GEOD-27065 | biostudies-arrayexpress