Molecular identification of spatially distinct anabolic responses to mechanical loading in murine cortical bone
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ABSTRACT:
PROVIDER: PRJNA867686 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20992900.fastq.gz | Fastqsanger.gz | |||
| SRR20992901.fastq.gz | Fastqsanger.gz | |||
| SRR20992902.fastq.gz | Fastqsanger.gz | |||
| SRR20992803.fastq.gz | Fastqsanger.gz | |||
| SRR20992903.fastq.gz | Fastqsanger.gz |
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Project description:Osteoporosis affects over 200 million women worldwide, one third of whom are predicted to suffer from an osteoporotic fracture in their lifetime. The most promising anabolic drugs involve administration of expensive antibodies. Because mechanical loading stimulates bone formation, our current data, using a mouse model, replicates the anabolic effects of loading in humans and may identify novel pathways amenable to oral treatment. Murine tibial compression produces axially-varying deformations along the cortical bone, inducing highest strains at the mid-diaphysis and lowest at the metaphyseal shell. To test the hypothesis that load-induced transcriptomic responses at different axial locations of cortical bone would vary as a function of strain magnitude, we loaded the left tibiae of 10wk female C57Bl/6 mice in vivo in compression, with contralateral limbs as controls. Animals were euthanized at 1, 3 or 24 h post-loading or loaded for 1 wk (n=4-5/group). Bone marrow and cancellous bone were removed, cortical bone was segmented into the metaphyseal shell, proximal diaphysis and mid-diaphysis, and load-induced differential gene expression and enriched biological processes were examined for the three segments. At each time point, the mid-diaphysis (highest strain) had the greatest transcriptomic response. Similarly, biological processes regulating bone formation and turnover increased earlier and to the greatest extent at the mid-diaphysis. Higher strain induced greater levels of osteoblast and osteocyte genes, whereas expression was lower in osteoclasts. Among the top differentially-expressed genes at 24-hours post-loading, seventeen had known functions in bone biology, of which twelve were present only in osteoblasts, three exclusively in osteoclasts, and two were present in both cell types. Based on these results, we conclude that murine tibial loading induces spatially-unique transcriptomic responses correlating with strain magnitude in cortical bone.
2022-08-12 | GSE210827 | GEO
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: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:Mechanical loading induces bone formation in young rodents, but mechanoresponsiveness is reduced with age. Glycolytic activity and mitochondrial dysfunction increase with age and may change bone mechanotransduction. To evaluate load-induced changes to bioenergetic activity in young and adult animals, we loaded the tibia of 10-wk and 26-wk female mice and examined transcriptomic responses at the mid-diaphysis, metaphyseal cortical shell, and cancellous core. Across all biological processes, oxidative phosphorylation and mitochondrial pathways were most often enriched with loading and had opposite enrichment in young and adult animals. Following loading, young animals had temporally-coordinated differential expression of mitochondrial-associated genes, with greatest expression at the mid-diaphysis. In adults, bioenergetic gene expression was lower compared to young animals.
2024-11-15 | GSE281942 | 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.
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:Anabolic resistance of skeletal muscle in cancer cachexia is caused by impaired IGF1 expression to mechanical loading
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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: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:Bioenergetic programs of cancellous and cortical bone are distinct and differ with age and mechanical loading
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