Expression data from young and aged BMSCs
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE116925 | GEO | 2018/08/15
REPOSITORIES: GEO
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Project description:During the aging process, bone marrow mesenchymal stem cells (BMSCs) exhibit declined osteogenesis accompanied by excess adipogenesis, which will lead to osteoporosis. Here we report that the H3K36 trimethylation, catalyzed by histone methyltransferase SETD2 regulates lineage commitment of BMSCs. Deletion of Setd2 in mBMSCs, through conditional Cre expression driven by Prx1 promoter, resulted in bone loss and marrow adiposity. Loss of Setd2 in BMSCs in vitro facilitated differentiation propensity to adipocytes rather than to osteoblasts. Through conjoint analysis of RNA-seq and ChIP-seq data, we identified a SETD2 functional target gene, Lbp, on which H3K36me3 was enriched, and its expression was affected by Setd2 deficiency. Furthermore, overexpression of LBP could partially rescue the lack of osteogenesis and enhanced adipogenesis resulted from the absence of Setd2 in BMSCs. Further mechanism study demonstrated that the trimethylation level of H3K36 could regulate Lbp transcriptional initiation and elongation. These findings suggest that H3K36 trimethylation mediated by SETD2 could regulate the cell fate of mesenchymal stem cells in vitro and in vivo, indicating that the regulation of H3K36me3 level by targeting SETD2 and/or the administration of downstream LBP protein may represent potential therapeutic way for new treatment in metabolic bone diseases, such as osteoporosis.
2018-11-08 | GSE120351 | GEO
Project description:During the aging process, bone marrow mesenchymal stem cells (BMSCs) exhibit declined osteogenesis accompanied by excess adipogenesis, which will lead to osteoporosis. Here we report that the H3K36 trimethylation, catalyzed by histone methyltransferase SETD2 regulates lineage commitment of BMSCs. Deletion of Setd2 in mBMSCs, through conditional Cre expression driven by Prx1 promoter, resulted in bone loss and marrow adiposity. Loss of Setd2 in BMSCs in vitro facilitated differentiation propensity to adipocytes rather than to osteoblasts. Through conjoint analysis of RNA-seq and ChIP-seq data, we identified a SETD2 functional target gene, Lbp, on which H3K36me3 was enriched, and its expression was affected by Setd2 deficiency. Furthermore, overexpression of LBP could partially rescue the lack of osteogenesis and enhanced adipogenesis resulted from the absence of Setd2 in BMSCs. Further mechanism study demonstrated that the trimethylation level of H3K36 could regulate Lbp transcriptional initiation and elongation. These findings suggest that H3K36 trimethylation mediated by SETD2 could regulate the cell fate of mesenchymal stem cells in vitro and in vivo, indicating that the regulation of H3K36me3 level by targeting SETD2 and/or the administration of downstream LBP protein may represent potential therapeutic way for new treatment in metabolic bone diseases, such as osteoporosis.
2018-11-08 | GSE120244 | GEO
Project description:Expression data from young and aged BMSCs
| PRJNA480646 | ENA
Project description:Pathological processes like osteoporosis or steroid-induced osteonecrosis of the hip are accompanied by increased bone marrow adipogenesis. Such disorder of adipogenic/osteogenic differentiation, which affects also bone marrow derived mesenchymal stem cells (BMSCs) contributes to bone loss during aging. Therefore, we investigated the effects of extracellular vesicles (EVs) isolated from human (h)BMSCs during different stages of osteogenic differentiation on osteogenic and adipogenic differentiation capacity of naïve hBMSCs.
2022-10-14 | PXD035845 | Pride
Project description:Mesenchymal stem cells (MSCs), known for their ability to differentiate into osteoblasts, play a pivotal role in bone metabolism. Prior to this study, we identified a novel lncRNA called MCP1 regulatory factor (MRF), which exhibits significant involvement in immune regulation of BMSCs. Moreover, we observed noticeable expression changes of MRF during the osteogenic differentiation of BMSCs. However, the exact role and underlying mechanism of MRF in the osteogenic differentiation of BMSCs remain elusive. QRT-PCR analysis was used to assess the expression of MRF. RNA interference and overexpression plasmids were employed to modulate MRF expression and observe changes in the osteogenic differentiation capacity of BMSCs. Downstream pathways involved in MRF-mediated regulation of BMSCs' osteogenic differentiation were predicted using transcriptome sequencing. The functionality of MRF in vivo was validated through a mouse tibial drilling defect model. In patients with osteoporosis, there is a conspicuous escalation in the expression of MRF within BMSCs. During the bone differentiation process of BMSCs, the MRF gradually diminishes over time. The knockdown of MRF amplifies the osteogenic differentiation of BMSCs, promoting an increased expression of bone-related proteins such as RUNX2, ALP, and COL1A1. Transcriptome sequencing and western blot indicated that cAMP/PKA/CREB signaling pathway was significantly activated after lncRNA-MRF knockdown. The mouse tibial drilling defect model demonstrates that the knockdown of MRF conspicuously advances ossification in vivo. MRF modulates the cAMP/PKA/CREB signaling axis through FSHR, thereby adjusting the ossification differentiation of BMSCs. Our research suggests that MRF may a potential target for bone related disorders.
2024-10-11 | GSE272041 | GEO
Project description:Vascular calcification often occurs with osteoporosis, a contradictory association called “calcification paradox”. We find that extracellular vesicles (EVs) released from aged bone matrix (AB-EVs) during bone resorption favor adipogenesis rather than osteogenesis of BMSCs and augment calcification of vascular smooth muscle cells (VSMCs). Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. To explore the involvement of miRNAs in the AB-EVs-induced promotion of adipocyte formation and vascular calcification, the Agilent miRNA array was conducted to compare the miRNA expression profiles in AB-EVs and YB-EVs from mouse bone specimens. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring functional miRNAs.
2022-02-15 | E-MTAB-11417 | biostudies-arrayexpress
Project description:Skeletal stem and progenitor cells (SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. To identify transcriptional changes that occur with aging we performed bulk RNA sequencing on young (3 month) and middle-aged (12 month) SSPCs.
2023-08-18 | GSE240286 | GEO
Project description:Young and Aged osteocytes in bone matrix secreted plenty of extracellular vesicles (EVs) with different functions. We found that EVs released from aged bone matrix (AB-EVs) during bone resorption favor adipogenesis rather than osteogenesis of BMSCs and augment calcification of vascular smooth muscle cells (VSMCs). In this work, we aim to detect the differential regulation microRNAs. Vascular calcification often occurs with osteoporosis, a contradictory association called “calcification paradox”. We find that extracellular vesicles (EVs) released from aged bone matrix (AB-EVs) during bone resorption favor adipogenesis rather than osteogenesis of BMSCs and augment calcification of vascular smooth muscle cells (VSMCs). Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. To explore the involvement of miRNAs in the AB-EVs-induced promotion of adipocyte formation and vascular calcification, the Agilent miRNA array was conducted to compare the miRNA expression profiles in AB-EVs and YB-EVs from mouse bone specimens. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring functional miRNAs.
2022-02-02 | GSE195931 | GEO
Project description:Skeletal stem and progenitor cells (SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. To identify transcriptional changes that occur with aging we performed bulk RNA sequencing on young (3 month) and middle-aged (12 month) SSPCs.
2023-08-18 | GSE240288 | GEO
Project description:The pathogenesis of osteoporosis (OP) is closely associated with the disrupted balance between osteogenesis and adipogenesis in bone marrow-derived mesenchymal stem cells (BMSCs). We analyzed published single-cell RNA sequencing (scRNA-seq) data to dissect the transcriptomic profiles of bone marrow-derived cells in OP, reviewing 56,377 cells across eight scRNA-seq datasets from femoral heads (osteoporosis or osteopenia n=5, osteoarthritis n=3). Seventeen genes, including carboxypeptidase M (CPM), were identified as key osteogenesis-adipogenesis regulators through comprehensive gene set enrichment, differential expression, regulon activity, and pseudotime analyses. In vitro, CPM knockdown reduced osteogenesis and promoted adipogenesis in BMSCs, while adenovirus-mediated CPM overexpression had the reverse effects. In vivo, intraosseous injection of CPM-overexpressing BMSCs mitigated bone loss in ovariectomized mice. Integrated scRNA-seq and bulk RNA sequencing analyses provided insight into the MAPK/ERK pathway's role in the CPM-mediated regulation of BMSC osteogenesis and adipogenesis; specifically, CPM overexpression enhanced MAPK/ERK signaling and osteogenesis. In contrast, the ERK1/2 inhibitor binimetinib negated the effects of CPM overexpression. Overall, our findings identify CPM as a pivotal regulator of BMSC differentiation, which provide new clues for the mechanistic study of OP.
2023-12-14 | GSE249471 | GEO