Characterize osteocyte transcriptome under control of PPARa
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE225595 | GEO | 2023/03/28
REPOSITORIES: GEO
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Project description:Characterize osteocyte transcriptome under control of PPARa
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Project description:Some cuboidal osteoblasts differentiate into bone-embedded, dendrite-bearing osteocytes through the poorly-understood process of osteocytogenesis. Here, we report that the transcription factor Sp7 plays an essential role in osteocytogenesis. Severe defects in bone integrity and osteocyte dendrite morphology are noted in mice lacking Sp7 at the stage of the osteoblast-to-osteocyte transition. In osteocytes, Sp7 controls expression of a neuronally-enriched gene network. Analysis of the osteocyte-specific Sp7 cistrome reveals distinct genomic binding motifs and target sites distinct from those in osteoblasts. Amongst osteocyte-specific Sp7 targets, the secreted peptide osteocrin rescues Sp7-deficient defects. Single-cell transcriptional profiling of cells undergoing osteocytogenesis identifies novel Sp7-dependent transitional cell types enriched in genes linked to human fracture risk. Finally, humans with an SP7 R316C mutation display osteocyte morphology defects similar to those observed in mouse models. These findings demonstrate that cuboidal osteoblasts use a neuronally-enriched Sp7/osteocrin gene expression program to differentiate into dendrite-bearing osteocytes.
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Project description:Some cuboidal osteoblasts differentiate into bone-embedded, dendrite-bearing osteocytes through the poorly-understood process of osteocytogenesis. Here, we report that the transcription factor Sp7 plays an essential role in osteocytogenesis. Severe defects in bone integrity and osteocyte dendrite morphology are noted in mice lacking Sp7 at the stage of the osteoblast-to-osteocyte transition. In osteocytes, Sp7 controls expression of a neuronally-enriched gene network. Analysis of the osteocyte-specific Sp7 cistrome reveals distinct genomic binding motifs and target sites distinct from those in osteoblasts. Amongst osteocyte-specific Sp7 targets, the secreted peptide osteocrin rescues Sp7-deficient defects. Single-cell transcriptional profiling of cells undergoing osteocytogenesis identifies novel Sp7-dependent transitional cell types enriched in genes linked to human fracture risk. Finally, humans with an SP7 R316C mutation display osteocyte morphology defects similar to those observed in mouse models. These findings demonstrate that cuboidal osteoblasts use a neuronally-enriched Sp7/osteocrin gene expression program to differentiate into dendrite-bearing osteocytes.
2021-09-20 | GSE154717 | GEO
Project description:Some cuboidal osteoblasts differentiate into bone-embedded, dendrite-bearing osteocytes through the poorly-understood process of osteocytogenesis. Here, we report that the transcription factor Sp7 plays an essential role in osteocytogenesis. Severe defects in bone integrity and osteocyte dendrite morphology are noted in mice lacking Sp7 at the stage of the osteoblast-to-osteocyte transition. In osteocytes, Sp7 controls expression of a neuronally-enriched gene network. Analysis of the osteocyte-specific Sp7 cistrome reveals distinct genomic binding motifs and target sites distinct from those in osteoblasts. Amongst osteocyte-specific Sp7 targets, the secreted peptide osteocrin rescues Sp7-deficient defects. Single-cell transcriptional profiling of cells undergoing osteocytogenesis identifies novel Sp7-dependent transitional cell types enriched in genes linked to human fracture risk. Finally, humans with an SP7 R316C mutation display osteocyte morphology defects similar to those observed in mouse models. These findings demonstrate that cuboidal osteoblasts use a neuronally-enriched Sp7/osteocrin gene expression program to differentiate into dendrite-bearing osteocytes.
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Project description:Purpose of arrays were to determine what the effect of deletion of Mbtps1 gene was on gene expression of osteocytes in bone in vivo. DMP1 cre driver was used to delete the Mbtps1 gene in osteocytes and osteoblasts in bone. We then isolated osteocyte enriched bone particles from 40 week old male mice to determine the effect of this deletion on gene expression. We have previously shown that Mbtps1 is needed for transcription of Phex, DMP1, and MEPE genes in osteoblasts in culture. Arrays showed these genes were reduced as expected in osteocytes in vivo. Controls represent osteocyte enriched bone from 40 week old littermates. Also, as expected, Mbtps1 expression was reduced in these knockout mice
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Project description:osteocyte is the mechanosensor in bone, taking up pivotal position in mediating the mechano-induced bone remodeling. Dimagnetic levitation has been used to stimulating a reduced gravity environment for studing the effects of changed gravity to different organisms.we constructed a superconducting magnet based platform with a large gradient high magnetic field(LG-HMF),which can provide three apparent gravity levels (?-g,1-g and 2-g). osteocytes are sensetive to gravitational changes, our aim is to explore what responses do osteocytes exists under different gravitational environments in gene level, together with filtering the up- and down-regulated genes. mouse osteocyte-like cell line MLO-Y4 were cultured under three different apparent gravity levels (?-g,1-g and 2-g) and normal gravity environment (control) for 48 hours, after which total RNA was extracted . And then RNA samples hybridized on affymetrix microarrays to obtain the whole genome expression profiles. the aim that we selected 48 hours as the cell culture time was to make a comparison with our previous researches of osteocytes.
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Project description:Osteocytes are long-lived, highly interconnected, terminally differentiated osteoblasts which reside within mineralized bone matrix. They constitute about 95% of adult bone cells and play important functions in the regulation of bone remodeling, phosphate homeostasis, and mechanical stimuli sensing and response. However, the role of osteocytes in the pathogenesis of congenital diseases of bone such as osteogenesis imperfecta (OI) is poorly understood. This study characterized in vivo transcriptional changes in osteocytes from the CrtapKO and oim/oim mouse models of OI, using RNA-sequencing on osteocyte-enriched cortical bone from femur and tibia. These models were chosen because they mimic two types of OI with different genetic mutations which result in distinct type I collagen defects. Hundreds of transcripts were dysregulated in either model of OI compared to WT, but 281 of these were similarly up- or down-regulated in both. Conversely, very few transcripts were differentially expressed between the CrtapKO and oim/oim mice, indicating that distinct alterations in type I collagen can lead to shared pathogenic processes and similar phenotypic outcomes. Bioinformatics analyses identified several critical hubs of dysregulation that were enriched in annotation terms such as development and differentiation, ECM and collagen fibril organization, cell adhesion, signaling, regulatory processes, pattern binding, chemotaxis, and cell projections. The data further indicated alterations in important signaling pathways such as WNT and TGF-β. Overall, our study suggested that the osteocyte transcriptome is broadly dysregulated in OI, that transcriptomic alterations in OI can be strikingly similar despite arising from different genetic mutations, and that the potential consequences of osteocyte dysregulation deserve further investigation.
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