Different exercise modalities have distinct effects on the transcriptome profile in the male rat femoral diaphysis
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE67787 | GEO | 2015/11/02
SECONDARY ACCESSION(S): PRJNA280937
REPOSITORIES: GEO
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Project description:Mechanical loading is a key determinant of bone mass, geometry and strength and is essential to maintain optimal skeletal health. We hypothesized that spontaneous low-impact exercise would affect global gene transcript levels in cortical bone of growing rats. We used RNA-Seq to analyse the transcriptome of the femoral mid-diaphysis in pre-pubertal male rats that were assigned to one of three exercise groups for 15 days: control (CON); bipedal stance (BPS); and wheel exercise (WEX). RNA-seq analysis identified 808 and 324 differentially expressed transcripts in the BPS and WEX animals, respectively. In WEX animals, the up-regulated transcripts were enriched for gene ontology terms associated with bone metabolism. Both BPS and WEX animals showed changes in transcripts that were enriched for muscle-related processes. However, in WEX these transcripts were down-regulated while in BPS such transcripts were up-regulated. Importantly, we observed that the exercise mode had diametrically opposite effects on transcripts for multiple genes within the integrin-linked kinase (ILK) and Ca2+ signalling pathways such that they were up-regulated in BPS and down-regulated in WEX. The findings are important for our understanding of possible ways in which different exercise regimens might affect bone when normal activities apply mechanical stimuli during post-natal growth and development. 24 weanling (21 day old) male Sprague-Dawley rats were assigned to three exercise groups .After the 15 day trial period, total RNA was extracted from the femoral diaphysis and mRNA profiles were analysed using RNA-seq
2015-11-02 | E-GEOD-67787 | 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:Studies have reported opposing effects of high-fat diet and mechanical stimulation on lineage commitment of the bone marrow stem cells. Yet, how the bone marrow modulates its gene expression in response to the combined effects of mechanical loading and a high-fat diet has not yet been addressed. We investigated whether early-life voluntary physical activity can modulate the effects of a high-fat diet on body composition, bone phenotype and bone marrow gene expression in male Sprague Dawley rats. We show that early-life high-fat diet positively affected body weight, total fat percentage and bone mass indices. In the bone marrow, early-life high-fat diet resulted in adipocyte hypertrophy and a pro-inflammatory and pro-adipogenic gene expression profile. Crucially, the bone marrow of the rats that undertook wheel exercise while on a high-fat diet retained a memory of the early-life exercise. This memory lasted at least 60 days after the cessation of the voluntary exercise and was manifest by: 1) the bone marrow adipocyte size of the exercised rats not exhibiting hypertrophy; and 2) genes associated with mature adipocyte function being down-regulated. Our results are consistent with the marrow adipose tissue having a unique and long-lasting response to high-fat feeding in the presence or absence of exercise.
2017-08-30 | GSE97376 | GEO
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: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:Physiological exercise leads to an activation of an distinct genetic program in the heart. During this process, we identified histone deacetlyase 4 (HDAC4) as an epigentic modifier, that regulates this adaptive process. To identify HDAC4 dependent genes that can are regulated after physiological stress, we investigated the cardiac gene expression in cardiomyocyte specific HDAC4 knockout animals and control animals after running exercise. We used microarrays to detail the global programme of gene expression underlying physiological cardiac adaption on exercise and identified distinct, histone deacetylase 4 dependent up-regulated genes during this process.
2017-06-07 | GSE72900 | GEO
Project description:Objective. Exercise is crucial for maintaining cartilage integrity and providing prophylaxis against the onset of osteoarthritis (OA). Here we systematically examined the exercise driven transcriptional activation/repression of genes from healthy articular cartilage to dissect the metabolic pathways responsible for its potential benefits. Methods. Healthy Sprague-Dawley rats were either not exercised (control) or subjected to daily exercise (low intensity treadmill walking) for 2, 5, or 15 days. Subsequently, articular cartilage from distal femoral heads was harvested, RNA extracted and the transcriptome-wide regulation of gene expression analyzed by Affymetrix microarray chips. Kyoto Encyclopedia of Genes and Genome (KEGG) database was used to identify the metabolic pathways regulated by exercise. Results. Microarray analysis of articular cartilage from exercised rats revealed two fold or greater up or down regulation of 926 transcripts for up to 15 days, as compared to control rat cartilage. The KEGG pathway analysis revealed that exercise transcriptionally activates/suppresses genes that encode proteins involved in regulating 123 metabolic pathways. These pathways control the biosynthesis of molecules associated with extracellular matrix, intermediate metabolites, cell signaling, cell growth and differentiation, cytoskeletal rearrangements, and inflammation including those associated with OA. Conclusions. Our findings highlight that exercise is a robust transcriptional regulator of a wide array of genes in the healthy cartilage. The actions of exercise collectively regulate metabolic pathways that are critical for strengthening cartilage while attenuating detrimental effects of proteolytic enzymes and inflammatory pathways to provide prophylaxis against inflammatory joint diseases. Sprague Dawley rats (n=5 per group, 12-14 weeks old females, Harlan Labs, IN) were housed at 5 animals/cage in individually ventilated cages with sterile Aspen bedding, and standard environmental enrichment. The cages were maintained at 12-h light/12-h dark cycle at 21°C in a pathogen free unit. All rats had ad libitum access to water and food and allowed normal cage activity. Animals randomly assigned to each group were either not exercised (Controls/Group I) or exercised (treadmill walking, 12 m/min for 45 min daily) for 2 (Group II), 5 (Group III), or 15 (Group IV) days13. Articular cartilage on the condyles of distal femurs were carefully dissected on ice under a stereomicroscope (10â15 mg/femur), immediately placed on dry ice and pulverized (3x30 seconds at 2500 RPM) in a Mikrodismembrator S (Sartorius, Germany). RNA was extracted using Trizol reagent (Invitrogen, CA), and RNA quality verified by a Bioanalyzer 2100 (Agilent, CA)13. The Whole Transcript (WT) cDNA Synthesis and Amplification Kit and WT Terminal Labeling Kit (Affymetrix, CA) were used for cDNA synthesis and labeling from 300 ng RNA template as recommended by the manufacturers. Labeled samples from 3 different rats from each group were hybridized to Affymetrix GeneChip Rat Gene 1.0 ST Array and scanned with GeneChip Scanner 3000 7G System (Microarray Shared Resource Facility, OSU Comprehensive Cancer Center)13.
2015-11-10 | E-GEOD-74898 | biostudies-arrayexpress
Project description:Objective. Exercise is crucial for maintaining cartilage integrity and providing prophylaxis against the onset of osteoarthritis (OA). Here we systematically examined the exercise driven transcriptional activation/repression of genes from healthy articular cartilage to dissect the metabolic pathways responsible for its potential benefits. Methods. Healthy Sprague-Dawley rats were either not exercised (control) or subjected to daily exercise (low intensity treadmill walking) for 2, 5, or 15 days. Subsequently, articular cartilage from distal femoral heads was harvested, RNA extracted and the transcriptome-wide regulation of gene expression analyzed by Affymetrix microarray chips. Kyoto Encyclopedia of Genes and Genome (KEGG) database was used to identify the metabolic pathways regulated by exercise. Results. Microarray analysis of articular cartilage from exercised rats revealed two fold or greater up or down regulation of 926 transcripts for up to 15 days, as compared to control rat cartilage. The KEGG pathway analysis revealed that exercise transcriptionally activates/suppresses genes that encode proteins involved in regulating 123 metabolic pathways. These pathways control the biosynthesis of molecules associated with extracellular matrix, intermediate metabolites, cell signaling, cell growth and differentiation, cytoskeletal rearrangements, and inflammation including those associated with OA. Conclusions. Our findings highlight that exercise is a robust transcriptional regulator of a wide array of genes in the healthy cartilage. The actions of exercise collectively regulate metabolic pathways that are critical for strengthening cartilage while attenuating detrimental effects of proteolytic enzymes and inflammatory pathways to provide prophylaxis against inflammatory joint diseases.
2015-11-10 | GSE74898 | GEO
Project description:Investigation of the SHIP1 (Inpp5d)-dependent and Rag2/Il2rg-dependent transcriptional changes in bone and osteoprogenitor cells cultures from murine strains with SHIP1 deficiency (Inpp5dm1Btlr/ m1Btlr, http://www.informatics.jax.org/allele/key/65037) and controls. Specifically, transcriptomic analysis was performed from femoral diaphysis from SHIPstyx/styx, SHIP1+/styx, wild-type (C57BL6/J), Rag2-/-/Il2rg-/-/SHIP1styx/styx, Rag2-/-/Il2rg-/-/SHIP1+/styx, and Rag2-/-/Il2rg-/-/SHIP1+/+ mice (n=3 for each genotype). Alternatively, osteoprogenitor cells isolated from bone marrow from the same genotypes as above were differentiated in vitro into primary osteoclasts in the presence or absence of RANKL. After 5 days, RNA was extracted from these cultures for transcriptomic analysis (n=3 for each genotype). Experimental Designs: Transcripts were analyzed in femoral diaphysis of SHIPstyx/styx, SHIP1+/styx, wild-type (C57BL6/J), Rag2-/-/Il2rg-/-/SHIP1styx/styx, Rag2-/-/Il2rg-/-/SHIP1+styx, and Rag2-/-/Il2rg-/-/SHIP1+/+ mice (n=3 for each genotype). Alternatively, transcripts were analyzed in primary osteoclast cultures from bone marrow cells isolated from SHIPstyx/styx, SHIP1+/styx, wild-type (C57BL6/J), Rag2-/-/Il2rg-/-/SHIP1styx/styx, Rag2-/-/Il2rg-/-/SHIP1+styx, and Rag2-/-/Il2rg-/-/SHIP1+/+ mice (n=3 for each genotype), which were supplemented or not with RANKL.
2024-02-21 | E-MTAB-13164 | biostudies-arrayexpress