Genome wide effects of vitamin C on in bone and during osteogenesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE138854 | GEO | 2022/06/10
REPOSITORIES: GEO
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Project description:Genome wide effects of vitamin C on in bone and during osteogenesis
| PRJNA577623 | ENA
Project description:Osteoclast differentiation and activation requires the presence of osteoblast-derived factors such as Macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kappaB ligand (RANKL). RANKL is influenced by osteotropic hormones such as calcitriol 1,25(OH)2D3 (vitamin D).The aim of this study is to evaluate the combined effect of vitamin D and M-CSF on murine bone marrow and on murine spleen cell, to define when the inhibitory effect of vitamin D plus M-CSF is maximum and what are the mechanisms involved in this inhibition. When murine bone marrow cells were cultured with 10-8 M vitamin D and 60 ng/ml M-CSF, there was a significant decrease in osteoclasts formation (3.13±3.44),compared to bone marrow cells cultured with vitamin D alone (80.86 ±45.02; p<0.05). Even when the amount of M-CSF added to the bone marrow cell culture was 1 ng/ml there was a 40% decrease in osteoclasts formation. Since bone marrow contains also stromal cells, we eliminate their influence by culturing murine spleen cells with 10-8 M vitamin D, 60 ng/ml M-CSF and RANKL 20 ng/ml. There was a significant decrease in osteoclasts formation (41±14.14) compared to spleen cells cultured with M-CSF and RANKL (215.67±46.44); p<0.05). These data lead to hypothesize that vitamin D and M-CSF together exert an inhibitory effect on osteoclast differentiation and development. To define the cellular mechanism involved in this inhibition we analyzed gene array data of bone marrow cells cultured with vitamin D and compare them with the cells cultured with vitamin D and M-CSF. Activation Toll like receptors after addition of vitamin D plus M-CSF to bone marrow cells appears to be involved in the inhibition of osteoclast differentiation. Keywords: parallel sample
2004-08-31 | GSE1587 | GEO
Project description:Bone development and repair depends on the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. MSCs can be differentiated towards osteoblasts in vitro, making these cells a convenient tool for investigation of osteogenesis. Molecular characterization of this process is relevant for the application of MSCs in skeletal regenerative medicine, and for understanding the deregulation of osteogenesis in bone disease. Cellular differentiation is driven by highly regulated changes in gene expression, which at the level of transcription is associated with DNA binding of transcriptional regulators and local changes in chromatin landscape. By sequencing of RNA (RNA-Seq) and immunoprecipitated chromatin (ChIP-Seq) we have characterized gene expression, histone modification changes and DNA binding of the bone master regulator RUNX2 in osteogenic differentiation. Data from the RNA-Seq experiment has also been deposited at ArrayExpress under accession number E-MTAB-1829 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1829/).
2013-09-01 | E-MTAB-1828 | biostudies-arrayexpress
Project description:Bone development and repair depends on the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. MSCs can be differentiated towards osteoblasts in vitro, making these cells a convenient tool for investigation of osteogenesis. Molecular characterization of this process is relevant for the application of MSCs in skeletal regenerative medicine, and for understanding the deregulation of osteogenesis in bone disease. Cellular differentiation is driven by highly regulated changes in gene expression, which at the level of transcription is associated with DNA binding of transcriptional regulators and local changes in chromatin landscape. By sequencing of RNA (RNA-Seq) and immunoprecipitated chromatin (ChIP-Seq) we have characterized gene expression, histone modification changes and DNA binding of the bone master regulator RUNX2 in osteogenic differentiation. Data from the RNA-Seq experiment has also been deposited at ArrayExpress under accession number E-MTAB-1829 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1829/).
2013-09-01 | E-MTAB-1829 | biostudies-arrayexpress
Project description:Recent studies have provided links between glutamine metabolism and bone remodeling, but little is known about its role in primary osteoporosis progression. We aimed to determine the effects of inhibiting glutaminase (GLS) on two types of primary osteoporosis and elucidate the related metabolism. To address this issue, age-related and ovariectomy (OVX)-induced bone loss mouse models were used to study the in vivo effects of CB-839, a potent and selective GLS inhibitor, on bone mass and bone turnover. We also studied the metabolic profile changes related with aging and GLS inhibition in primary bone marrow stromal cells (BMSC) and that related with OVX and GLS inhibition in primary bone marrow-derived monocytes (BMM). Besides, we studied the possible metabolic processes mediating GLS blockade effects during aging-impaired osteogenic differentiation and RANKL-induced osteoclast differentiation respectively via in vitro rescue experiments. We found that inhibiting GLS via CB-839 prevented OVX-induced bone loss while aggravated age-related bone loss. Further investigations showed that effects of CB-839 treatment on bone mass were associated with alterations of bone turnover. Moreover, CB-839 treatment altered metabolic profile in different orientations between BMSC of aged mice and BMM of ovariectomized mice. In addition, rescue experiments revealed that different metabolic processes mediated glutaminase blockade effects between aging-impaired osteogenic differentiation and RANKL-induced osteoclast differentiation. Taken together, our data demonstrated the different outcomes caused by CB-839 treatment between two types of osteoporosis in mice, which were tightly connected to the suppressive effects on both aging-impaired osteoblastogenesis and OVX-enhanced osteoclastogenesis mediated by different metabolic processes downstream of glutaminolysis.
2024-06-17 | MTBLS9415 | MetaboLights
Project description:genome wide methylation data include: MeDIP-seq and MRE-seq in Vitamin D deficient and sufficient bone marrow cells
2023-08-21 | GSE157195 | GEO
Project description:We previously found that KLF4, a gene highly expressed in adult prostate stem cells, blocks the progression of indolent intraepithelial prostatic lesions into aggressive and rapidly growing tumors. To test whether this anti-cancer effect of KLF4 can also prevent prostate cancer-induced damage to the bone, we ablated KLF4 in human PC3 prostate cancer cells using CRISPR/Cas9-mediated genome editing and compared their behavior to null cells transduced with a DOX inducible KLF4 expression system. KLF4 re-expression inhibited growth of PC3 null cells in monolayer and as colonies in soft agar in a dose-dependent manner. When injected into the mouse femurs, PC3 null cells proliferated rapidly, forming very large, invasive and osteolytic tumors. Induction of KLF4 expression in PC3 null cells immediately after their intra-femoral inoculation blocked the development of tumors while preserving the normal bone architecture. KLF4 re-expression in established PC3 bone tumors inhibited osteolytic effects of PC3 null cells, preventing bone fractures and inducing a significant osteogenic response with regions of new bone formation. Transcriptome analyses of PC3 cells with no or high KLF4 expression revealed KLF4-dependent osteolytic or osteogenic transcriptional programs, respectively. Importantly, these KLF4-dependent functions significantly overlapped with metastatic prostate cancers in patients.
2019-05-09 | GSE117965 | GEO
Project description:Osteoradionecrosis of the jaw (ORNJ) is a complication after head and neck radiotherapy that severely affects patients’ quality of life. Currently, an overall understanding of microenvironmental factors of ORNJ is still lacking. Here, we reveal the activation of taurine metabolism in irradiated mandibular stromal cells with scRNA-Seq and the decrease of taurine in irradiated bone marrow mesenchymal stromal cells (BMSCs) with metabolomics. Compared to the unirradiated BMSCs, the taurine uptake of irradiated BMSCs increases. The taurine concentration in peripheral blood and jaws of irradiated mice are significantly lower than the unirradiated mice. Supplementation of taurine promotes osteogenic differentiation, decreases oxidative stress and DNA damage of irradiated BMSCs. Oral administration of taurine significantly promotes survival rate of irradiated mice and promotes osteogenesis of irradiated jaws. Our study sheds light on the role of taurine during the recovery of radiation-induced jaw injury, suggesting a potential non-invasive therapeutic means to combat ORNJ.
2024-07-08 | MTBLS10284 | MetaboLights
Project description:This SuperSeries is composed of the following subset Series:; GSE12264: Gene Expression Profile of Osteogenic Cells Derived from Human Bone Marrow and Trabecular Bone I; GSE12265: Gene Expression Profile of Osteogenic Cells Derived from Human Bone Marrow and Trabecular Bone II; GSE12266: Gene Expression Profile of Osteogenic Cells Derived from Human Bone Marrow and Trabecular Bone III Experiment Overall Design: Refer to individual Series
2008-10-21 | E-GEOD-12267 | biostudies-arrayexpress
Project description:In this study, we found that Fgf9 regulates the bone-fat balance by modulating the cell fate determination of BMSCs. Histology and micro-CT analysis demonstrate that Fgf9 S99N mutation (loss-of-function) significantly inhibited the formation of bone marrow adipose tissue (BMAT) in adult mice and alleviated the ovariectomized (OVX) induced bone loss and BMAT accumulation. In vitro cytodifferentiation assays unveiled that the Fgf9 S99N mutation hindered adipogenesis while promoting osteogenesis in BMSCs. Furthermore, recombinant FGF9 stimulation and Fgf9 overexpression in BMSCs demonstrated that Fgf9 significantly promoted adipocyte formation and inhibited osteogenesis in vitro and in vivo. Cytodifferentiation assays at various stages of BMSC differentiation indicated that FGF9 altered the osteogenic and adipogenic potential of BMSCs, particularly during the early stages of differentiation. Transcriptomic and gene expression analyses demonstrated that FGF9 significantly upregulated the expression of adipogenic genes while downregulating osteogenic gene expression at both mRNA and protein levels. KEEG analysis revealed and in vitro differentiation assays with specific inhibitors confirmed that FGF9 modulated bone-fat balance by inhibiting osteogenesis via the MAPK/ERK pathway and promoting adipogenesis by activating the PI3K/AKT and Hippo pathways.
2024-07-17 | GSE252394 | GEO