Similar Datasets
Project description:There is an increasing clinical evidence that obesity exerts deleterious effects on the skeleton. While obesity coexists with estrogen deficiency in postmenopausal women, their combined effects on the skeleton are poorly studied. Thus, we investigated the impact of high-fat diet (HFD) on bone and metabolism of ovariectomized (OVX) female mice (C57BL/6J). OVX or sham operated mice were fed either HFD (60%fat) or normal diet (ND) (10%fat) for 12 weeks. HFD-OVX group exhibited pronounced increase in body weight (~86% in HFD and ~122% in HFD-OVX, p<0.0005) and impaired glucose tolerance. Bone microCT-scanning revealed a pronounced decrease in trabecular bone volume/total volume (BV/TV) in HFD-OVX (15.6±0.48% in HFD and 37.5±0.235% in HFD-OVX, p<0.005) and expansion of bone marrow adipose tissue (BMAT) (+60.7±9.9% in HFD vs +79.5±5.86% in HFD-OVX, p<0.005). Mechanistically, HFD-OVX treatment led to upregulation of genes markers of senescence, bone resorption, adipogenesis and inflammation and downregulation of gene markers of bone formation and bone development. Similarly, HFD- OVX treatment resulted in significant changes in bone tissue levels of Purine/Pyrimidine and Glutamate metabolisms, known to play a regulatory role in bone metabolism. Obesity and estrogen deficiency exert combined deleterious effects on bone resulting in accelerated cellular senescence, expansion of BMAT and impaired bone formation leading to decreased bone mass. Our results suggest that obesity may increase bone fragility in post-menopausal women.
2022-12-05 | GSE194075 | GEO
Project description:To search for the role of microRNAs in postmenopausal osteoporosis, we used an experimental ovariectomized (OVX) mice moldel. We operated ovariectomy in 3-month-old C57BL/6 mice and collected the femurs after 6months to perform miRNA microarray analysis to identify dysregulated microRNAs.
2018-01-27 | GSE109705 | GEO
Project description:To examine the effect of E2 treatment for the miRNA expression, at 15 week old, female wiled type mice were ovariectomized, and after one week, estradiol (E2) was delivered at a concentration of 0.050 mg/kg body weight/day. 24 hours after chemical treatment, uteruses from mice treated with or without E2 were dissected. Two group experiment (WT-OVX and WT-OVX-E2) three replicates per condition
2010-06-24 | E-GEOD-13858 | biostudies-arrayexpress
Project description:PTH is an osteoanabolic for treating osteoporosis but its potency wanes. Disabling the transcription factor nuclear matrix protein 4 (Nmp4) in healthy, ovary-intact mice enhances bone response to PTH and bone morphogenetic protein 2 and protects from unloading-induced osteopenia. These Nmp4-/- mice exhibit expanded bone marrow populations of osteoprogenitors and supporting CD8+ T cells. To determine whether the Nmp4-/- phenotype persists in an osteoporosis model we compared PTH response in ovariectomized (ovx) wild-type (WT) and Nmp4-/- mice. To identify potential Nmp4 target genes, we performed bioinformatic/pathway profiling onNmp4chromatin immunoprecipitation sequencing (ChIP-seq) data. Mice (12 weeks old) were ovx or sham operated 4 weeks before the initiation of PTH therapy. Skeletal phenotype analysis included microcomputed tomography, histomorphometry, serum profiles, fluorescence-activated cell sorting and the growth/mineralization of cultured WT and Nmp4-/- bone marrow mesenchymal stem progenitor cells (MSPCs). ChIP-seq data were derived using MC3T3-E1 preosteoblasts, murine embryonic stem cells, and 2 blood cell lines. Ovx Nmp4-/- mice exhibited an improved response to PTH coupled with elevated numbers of osteoprogenitors and CD8+ T cells, but were not protected from ovx-induced bone loss. Cultured Nmp4-/- MSPCs displayed enhanced proliferation and accelerated mineralization. ChIP-seq/gene ontology analyses identified target genes likely under Nmp4 control as enriched for negative regulators of biosynthetic processes. Interrogation of mRNA transcripts in nondifferentiating and osteogenic differentiating WT and Nmp4-/- MSPCs was performed on 90 Nmp4 target genes and differentiation markers. These data suggest that Nmp4 suppresses bone anabolism, in part, by regulating IGF-binding protein expression. Changes in Nmp4 status may lead to improvements in osteoprogenitor response to therapeutic cues.
2018-04-05 | GSE112693 | GEO
Project description:The peri- and postmenopausal periods in women are associated with decreases in circulating estrogen levels, marked acceleration of age-related bone loss and increased risk of fracture. However, despite the clinical importance of postmenopausal bone loss, our molecular understanding of this process is incomplete. Here, we used co-expression network analysis to gain novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause. Expression profiles from intact and OVX mice from a panel of inbred strains were used to generate a co-expression network consisting of 29 modules. Genes in network module 25 were decreased by OVX in all strains. Module 25 was enriched for genes involved in the response to oxidative stress, a process known to be an upstream causal factor for OVX-induced bone loss. It was also found that module 25 homologs were co-expressed in human bone marrow and were enriched for genes with evidence of genetic association with bone mineral density (BMD) in women. Alpha synuclein (Snca) was the most highly connected “hub” genes in module 25 and its in vivo knockout resulted in a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the targeted alteration of genes in specific network modules, including module 10. Our results identify a gene module associated with OVX-induced bone loss and demonstrate that Snca regulates ovariectomy-induced bone loss by controlling bone network dynamics.
2016-12-01 | GSE68302 | GEO
Project description:The peri- and postmenopausal periods in women are associated with decreases in circulating estrogen levels, marked acceleration of age-related bone loss and increased risk of fracture. However, despite the clinical importance of postmenopausal bone loss, our molecular understanding of this process is incomplete. Here, we used co-expression network analysis to gain novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause. Expression profiles from intact and OVX mice from a panel of inbred strains were used to generate a co-expression network consisting of 29 modules. Genes in network module 25 were decreased by OVX in all strains. Module 25 was enriched for genes involved in the response to oxidative stress, a process known to be an upstream causal factor for OVX-induced bone loss. It was also found that module 25 homologs were co-expressed in human bone marrow and were enriched for genes with evidence of genetic association with bone mineral density (BMD) in women. Alpha synuclein (Snca) was the most highly connected “hub” genes in module 25 and its in vivo knockout resulted in a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the targeted alteration of genes in specific network modules, including module 10. Our results identify a gene module associated with OVX-induced bone loss and demonstrate that Snca regulates ovariectomy-induced bone loss by controlling bone network dynamics.
2016-12-01 | GSE68303 | GEO
Project description:Objective—Overexpression or administration of sclerostin has been reported to have atheroprotective and anti-inflammatory effects in apolipoprotein E knockout (ApoE KO) mice infused with angiotensin II; however, effects of sclerostin inhibition on these processes are not known. This study examined the effects of sclerostin inhibition with a sclerostin antibody on transcriptional changes in the aortic arch, associated morphological changes in aortic atherosclerotic plaques, and circulating markers of inflammation in ApoE KO ovariectomized (OVX) mice fed a high-fat diet. Approach and Results—Sclerostin antibody or vehicle was administered by subcutaneous injection once weekly for 3, 8, or 16 weeks to ApoE KO-OVX and wild-type-OVX mice fed a high-fat diet. As a comparator, alendronate or saline was administered twice weekly for 16 weeks to ApoE KO-OVX mice fed a high-fat diet. Sclerostin antibody had no effect on aortic total or mineralized plaque volume, determined by microcomputed tomography. Sclerostin antibody had no meaningful effects on plaque histopathology or systemic markers of inflammation or endothelial/platelet activation. Transcriptional analysis of the aortic arch revealed significant gene expression and signaling pathway changes in ApoE KO mice compared with wild-type, consistent with the genotype and atheroprogression, that were not affected by sclerostin antibody treatment. Alendronate treatment did not alter plaque volume or histopathology. Conclusions—This study shows that inhibition of sclerostin by sclerostin antibody does not promote atheroprogression or affect systemic markers of inflammation in the high-fat diet ApoE KO-OVX mouse model and does not alter the expression of genes/pathways implicated in atherosclerosis.
2020-05-01 | GSE130995 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE106: OVX/P4/UTX 129/SvImJ WT A; GSE107: OVX/P4/UTX 129/SvImJ WT B Experiment Overall Design: Refer to individual Series. Female mice used were 129/SvImJ wildtype (Jackson Lab), 10-16 weeks of age. 14 days after ovariectomy, mice were injected subcutaneously with progesterone dissolved in sesame oil (Sigma; 0.2mg/0.1mL/mouse), followed by sacrifice and removal of uterine horns at various times after injection. 8 uterine horns from 4 mice were pooled to form one sample. Total RNA preparation, cRNA labeling and hybridization were performed according to recommendations by Affymetrix.
2007-11-15 | E-GEOD-6440 | biostudies-arrayexpress
Project description:Uterine stromal cells were isolated from OVX Atg7f/f and Atg7d/d mice injected with oil or E2. Each group was pooled from 4 OVX mice and the experiment was run in duplicates. RNA quality was assessed by Agilent 2100 bioanalyzer using the RNA 6000 Nano Chip (Agilent Technologies, Amstelveen, The Netherlands), and RNA quantification was performed using ND-2000 Spectrophotometer (ThermoFisher Scientific). Total RNA (1 μg) was prepared and processed for high-throughput sequencing using NextSeq 500 (Illumina, San Diego, CA, USA) and data profiling was serviced by e-biogen (Seoul, Korea).
2019-12-31 | GSE131304 | GEO