MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation [osteoblast]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE63724 | GEO | 2014/12/02
SECONDARY ACCESSION(S): PRJNA268913
REPOSITORIES: GEO
Similar Datasets
Project description:We identified microRNA-188 differentially expressed in the BMSCs of aged and young mice and influenced on BMSCs differentiation with ageing. Then we used microarrays to detail the adipogenic gene expression during adipogenic differention of BMSCs from 188KO mice.
2014-12-02 | GSE63723 | GEO
Project description:To identify microRNAs which differentially expressed in the BMSCs of aged and young mice and and investigate its influences on BMSCs differentiation with ageing. The microRNAs expressions of BMSCs from 3 aged mice and 3 young mice were measured.
2014-04-29 | E-GEOD-57127 | biostudies-arrayexpress
Project description:To identify microRNAs which differentially expressed in the BMSCs of aged and young mice and and investigate its influences on BMSCs differentiation with ageing.
2014-04-29 | GSE57127 | GEO
Project description:Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra-bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss.
| S-EPMC4396470 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2014-12-02 | GSE63725 | GEO
Project description:Osteoporosis is a chronic age-related disease. During aging, bone marrow-derived mesenchymal stem cells (BMSCs) display increased adipogenic, along with decreased osteogenic, differentiation capacity. The aim of the present study was to investigate the effect of calcitonin gene-related peptide (CGRP) on the osteogenic and adipogenic differentiation potential of BMSC-derived osteoblasts. Here, we found that the level of CGRP was markedly lower in bone marrow supernatant from aged mice compared with that in young mice. In vitro experiments indicated that CGRP promoted the osteogenic differentiation of BMSCs while inhibiting their adipogenic differentiation. Compared with vehicle-treated controls, aged mice treated with CGRP showed a substantial promotion of bone formation and a reduction in fat accumulation in the bone marrow. Similarly, we found that CGRP could significantly enhance bone formation in ovariectomized (OVX) mice in vivo. Together, our results suggested that CGRP may be a key regulator of the age-related switch between osteogenesis and adipogenesis in BMSCs and may represent a potential therapeutic strategy for the treatment of age-related bone loss.
| S-EPMC8187789 | biostudies-literature
Project description:Escherichia coli strain:188 | isolate:188 Genome sequencing
| PRJNA666802 | ENA
Project description:The treatment of bone defects caused by infection, trauma or neoplasms remains a clinical challenge. Autologous bone transplantation is limited by availability, donor site morbidity and surgical risk factors. This has given rise to stromal/stem-cell based therapy. Bone marrow derived stromal cells (BMSCs) have been studied to a large extent and show high regenerative potential but their use is limited by availability, donor site morbidity and the relatively low cell yield as they represent only <0.1% of cell harvested from bone marrow aspirate. At the same time, they are the closest mesenchymal stromal cells for bone tissue engineering given their tissue origin and, unlike other mesenchymal stromal cells, can support the formation of hematopoietic marrow. Adipose tissue derived stromal cells (ASCs) as part of the stromal vascular fraction of adipose tissue can as well undergo osteogenic differentiation but can be additionally isolated in a sufficient quantity from lipoaspirate after liposuction of abundant subcutaneous fat tissue. Here, it has been shown that there are no major differences in regard to proliferation or differentiation capacity of ASCs derived from subcutaneous fat of different anatomical regions. It has been shown that BMSCs are more prone to senescence during expansion and passage than ASCs and that ageing impacts proliferative capabilities of BMSCs more than that of ASCs while it has also been reported that osteogenic differentiation capacity is least impacted by age. Multiple studies have compared the characteristics of these two mesenchymal stromal cells in regard to bone tissue engineering in vitro. Most studies point to inferior extracellular matrix mineralization and lower expression of key osteogenic transcription markers like Runx2 in osteogenic differentiated ASCs compared to BMSCs. On the other hand, a study by Rath et al. found contrary results using particular culturing conditions like 3D bioglass scaffolds. An intraindividual comparison of human MSCs of three donors cultured on decellularized porcine bone confirmed superior osteogenic capacity of BMSCs compared to ASCs. In contrast to BMSCs, ASCs were not able to induce heterogenic ossification in a mouse model. In a sheep tibia defect model application of BMSCs resulted in a significantly higher amount of newly formed bone tissue. Importantly, Osteogenic differentiated ASCs do not support the formation of a hematopoietic marrow. Proteomics enables large-scale analysis of proteins present in a cell type and can be used to identify differentially regulated key proteins in a comparative approach. A comparative proteomic analysis of BMSCs and ASCs by Roche et al. in 2009 identified 556 proteins with 78% of these not being differentially regulated between these two cell populations, regarded as high similarity. Another comparative proteomic study of 2016 by Jeon et al. found 90 differentially regulated proteins out of 3000 total identified proteins. Both studies do not specify a number of different tissue donors and in part using cell lines. Looking for differences upon osteogenic differentiation, transcriptomic comparison of osteogenic differentiated porcine ASCs and BMSCs has been performed, resulting in 21 differentially expressed genes after 21 days of osteogenic culture conditions. Still, it remains unanswered, which are the key distinctive features of osteogenic differentiated ASCs and BMSCs at protein level that might help address the abovementioned weaknesses of ASCs in bone tissue engineering/regeneration for translational research. To overcome this need, an intraindividual comparative DIA based proteomic analysis of osteogenic differentiated human BMSC and ASCs was performed in this study.
2021-06-09 | PXD015223 | Pride
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:Background: Dicalcium cilicate (C2S) is a potent biomaterial for bone regeneration application. Circular RNA (circRNAs) plays crucial role in osteogenic differentiation of mesenchymal stem cells (MSCs) and bone defect healing. In this study, we aim to elucidate the differential expression of circ_RNAs and mRNAs in C2S-treated MSCs, the role of circ_1983 in C2S-mediated bone regeneration, and its mechanism. Methods: The effect of C2S on osteogenic differentiation of mice bone marrow-derived MSCs (BMSCs) and rat cranial bone defect healing were analyzed. Differential expression of circ-RNAs and mRNAs in C2S-treated BMSCs were profiled by RNA-sequencing. The interaction between circ_1983 and miR-6931 was confirmed by pull-down and dual luciferase reporter assays. ceRNA function of circ_1983 via sponging miR-6931 and targeting Gas7 mRNA expression in BMSCs was analyzed by miRanda (http://www.microrna.org/microrna/). Role of circ_1983 in C2S-induced osteogenic differentiation of BMSCs was analyzed by shRNA-mediated knockdown of circ_1983. Results: C2S enhanced osteogenic differentiation of BMSCs and bone defect healing. CircRNAs (total 1384) and mRNAs (total 1725) were differentially upregulated in C2S-treated BMSCs. Upregulated circRNAs and ceRNA-interaction networks were associated with osteogenesis-related signaling pathways, i.e. MAPK, PI3K-Akt. RNA-sequencing and qRT-PCR results confirmed upregulation of circ_1983 in C2S-tretaed BMSCs. Circ_1983 showed ceRNA effect by sponging miR-6931 and overexpressing Gas mRNA that enhanced Runx2 expression and promoted osteogenic differentiation of BMSCs. Knockdown of circ_1983 inhibited the C2S-induced osteogenic differentiation of BMSCs. Interpretation: C2S-induced circ_1983 upregulation in BMSCs sponges miR-6931 and targets Gas7 gene to enhance Runx2 expression thereby promotes osteogenic differentiation and bone regeneration.
2021-04-12 | GSE140273 | GEO