MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE57127 | GEO | 2014/04/29
SECONDARY ACCESSION(S): PRJNA245525
REPOSITORIES: GEO
Similar Datasets
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:We identified microRNA-188 differentially expressed in the BMSCs of aged and young mice and influented on BMSCs differentiation with ageing. Then we used microarrays to detail the osteogenic gene expression during osteogenic differention of BMSCs from 188KO mice.
2014-12-02 | GSE63724 | GEO
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: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:Ageing-related delays in wound healing are well-documented in both human and animal models. However, the mechanisms underlying this impairment in healing progression are not fully understood. In this study, we characterised ageing-associated changes to the structure and function of the skin in young and aged mice and investigated the cellular differences that impacted the progression of wound healing. Full-thickness wounds created on the dorsum of C57BL/6J young and aged mice were excised on Day 0, Day 3 and Day 7 post-wounding for analysis by immunohistochemistry, flow cytometry, RNA sequencing. Our data revealed that macrophages were significantly reduced in aged wounds in comparison to young. Functional transcriptomic analyses showed that macrophages from aged wounds exhibited significantly reduced expression of cell cycle, DNA replication, and repair pathway genes. Furthermore, we uncovered an elevated pro-inflammatory gene expression program in the aged macrophages linked to poor inflammation resolution and excessive tissue damage observed in aged wounds. Altogether, our work provides insights into how poorly healing aged wounds are phenotypically defined by the presence of macrophages with reduced proliferative capacity and an exacerbated inflammatory response, both of which are pathways that can be targeted to improve healing in the elderly.
2022-06-24 | GSE199763 | GEO
Project description:Described here is the application of thermodynamic stability measurements to study age-related differences in the protein folding and stability of proteins in a rodent model of ageing. Using the Stability of Proteins from Rates of Oxidation (SPROX) technique the thermodynamic stability profiles were generated for 807 proteins in brain cell lystaes from mice, aged 6- (n=7) and 18-months (n=9). The biological variability of the protein stability measurements was low and within the experimental error of SPROX. A total of 83 protein hits were detected with age-related stability differences in the brain samples. Remarkably, the large majority of the brain protein hits were destabilized in the old mice, and the hits were enriched in proteins that have slow turnover rates (p <0.07). Furthermore, 70% of the hits have been previously linked to ageing or age-related diseases. These results help validate the use of thermodynamic stability measurements to capture relevant age-related proteomic changes, and they establish a new biophysical link between these proteins and ageing.
2016-12-22 | PXD005184 | Pride
Project description:Aging leads to the disruption of the homeostatic balance of multiple biological systems. In bone marrow multipotent mesenchymal cells undergo differentiation into various anchorage-dependent cell types, including osteoblasts and adipocytes. With age as well as with treatment of antidiabetic drugs such as thiazolidinediones, mesenchymal cells favor differentiation into adipocytes, resulting in an increased number of adipocytes and a decreased number of osteoblasts, causing osteoporosis. The mechanism behind this differentiation switch is unknown. Here we show an age-related decrease in the expression of Maf in mouse mesenchymal cells, which regulated mesenchymal cell bifurcation into osteoblasts and adipocytes by cooperating with the osteogenic transcription factor Runx2 and inhibiting the expression of the adipogenic transcription factor Pparg. The crucial role of Maf in both osteogenesis and adipogenesis was underscored by in vivo observations of delayed bone formation in perinatal Maf(-/-) mice and an accelerated formation of fatty marrow associated with bone loss in aged Maf(+/-) mice. This study identifies a transcriptional mechanism for an age-related switch in cell fate determination and may provide a molecular basis for novel therapeutic strategies against age-related bone diseases.
| S-EPMC2947225 | biostudies-literature
Project description:A deficit in synaptic plasticity is one of the many changes that occurs with age. Specifically the archetypal model of plasticity, long-term potentiation (LTP), is reduced in hippocampus of middle-aged and aged animals. Several factors are likely to contribute to this deficit including morphological changes like a net loss of neurons and loss of synapses with the consequent changes in receptor signalling. However it is also clear that ageing is associated with development of oxidative stress, and also inflammatory stress which is typified by increased activation of microglia. Recent evidence has indicated that probiotics exert anti-inflammatory in the gut. Specifically VSL#3, a proprietary probiotic comprising 8 Gram-positive bacterial strains, decreased markers of inflammation in the colon in an animal model of colitis. We considered that its anti-inflammatory effects might extend to brain and therefore that treatment of aged rats with VSL#3 might attenuate the age-related deficit in LTP. The evidence indicates that LTP was impaired in control-treated aged rats but sustained in aged rats which received VSL#3. This was accompanied by a modest decrease in markers of microglial activation and an increase in BDNF and synapsin . The microarray analysis demonstrated that VSL#3 treatment induces changes also in the expression of some brain genes. four sample groups each representing a certain treatment condition of young or adult male Han Wistar rats
2014-04-02 | E-GEOD-51381 | biostudies-arrayexpress