Phosphate promotes osteogenic differentiation through non-canonical Wnt signaling pathway in human mesenchymal stem cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE211513 | GEO | 2022/08/24
REPOSITORIES: GEO
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Project description:Phosphate promotes osteogenic differentiation through non-canonical Wnt signaling pathway in human mesenchymal stem cells
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Project description:Human bone marrow-derived mesenchymal stem/stromal cells (hBM MSCs) have multiple functions, critical for skeletal formation and function. Their functional heterogeneity, however, represents a major challenge for their isolation and in developing and potency and release assays to predict their functionality prior to transplantation. Additionally, potency, biomarker profiles and defining mechanisms of action in a particular clinical setting are increasing requirements of Regulatory Agencies for release of hBM MSCs as Advanced Therapy Medicinal Products (ATMPs) for cellular therapies. Since the healing of bone defects in larger bone grafts depends on the coupling of new blood vessel formation with osteogenesis, we hypothesised that a correlation between the osteogenic and vascular supportive potential of individual hBM MSC-derived CFU-F (colony forming unit-fibroblastoid) clones might exist. We tested this by assessing the lineage (i.e. adipogenic {A}, osteogenic {O} and/or chondrogenic {C}) potential of individual hBM MSC-derived CFU-F clones and determining if their osteogenic {O} potential correlated with their vascular supportive profile in vitro using lineage differentiation assays, endothelial-hBM MSC vascular co-culture assays and transcriptomic (RNAseq) analyses. Our results demonstrate that the majority of CFU-F (95%) possessed tri-lineage, bi-lineage or uni-lineage osteogenic capacity, with 64% of the CFU-F exhibiting tri-lineage AOC potential. We found a correlation between the osteogenic and vascular tubule supportive activity of CFU-F clones, with the strength of this association being donor dependent. RNAseq of individual clones defined gene fingerprints relevant to this correlation.
2018-12-26 | GSE117844 | GEO
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:To see the effect of zoledronate on the osteogenic differentiation of human mesenchymal stem cells. Cells were first cultured in normal media until enough cells were obtained. Then the cells were differentiated into ostepbalst under the effect of low concentration of zoledronate.
2020-01-16 | E-MTAB-7459 | biostudies-arrayexpress
Project description:Sexual dimorphism in osteogenic differentiation
| PRJNA768873 | ENA
Project description:Purpose: To analyze cardiac fibroblasts gene expression at different time following induction of osteogenic differentiation Methods: Freshly isolated cardiac fibroblasts (Passage 0 or passage 1) were plated at a density of 2.5 x 104 cells/cm2 in growth medium. After overnight incubation, osteogenesis was induced using differentiation medium (α-MEM supplemented with 10% FBS, 10 nM dexamethasone (Sigma, D4902), 20 mM β-glycerol phosphate (Sigma, G9422), and 50 μM L-ascorbic acid (Sigma, A4403). Cardiac fibroblasts harvested at Day0 (before differentiation medium treatment), Day7, Day14 and Day21 were used for RNA sequencing. Results: Cardiac fibroblasts harvested at different time points following induction of differentiation revealed clusters of genes whose expression was significantly altered in a temporal specific manner. Genes regulating cell cycle that were highly expressed in undifferentiated cardiac fibroblasts were down-regulated at the onset of differentiation and remained at low expression levels throughout the duration of osteogenic differentiation, consistent with the principle that induction of differentiation is associated with reduced rates of proliferation. In contrast, genes that were minimally expressed in cardiac fibroblasts were induced in a specific temporal manner during the course of osteogenic differentiation and included sets of genes known to regulate inflammation, extracellular matrix proteins and cell metabolism. Conclusions: Cardiac fibroblasts subjected to osteogenic differentiation progressively adopted an osteogenic signature.
2016-11-07 | GSE87836 | GEO
Project description:Phosphate-solubilizing bacteria (PSB) have the ability to dissolve insoluble phosphate and enhance soil fertility. However, the growth and mineral phosphate solubilization of PSB could be affected by exogenous soluble phosphate and the mechanism has not been fully understood. In the present study, the growth and mineral phosphate-solubilizing characteristics of PSB strain Burkholderia multivorans WS-FJ9 were investigated at six levels of exogenous soluble phosphate (0, 0.5, 1, 5, 10 and 20 mM). The WS-FJ9 strain showed better growth at high levels of soluble phosphate. The phosphate-solubilizing activity of WS-FJ9 reduced as the soluble phosphate concentration increased, as well as the production of pyruvic acid. Transcriptome profiling of WS-FJ9 at three levels of exogenous soluble phosphate (0, 5 and 20 mM) identified 446 differentially expressed genes, among which 44 genes were continuously up-regulated when soluble phosphate concentration increased and 81 genes were continuously down-regulated. Some genes related to cell growth were continuously up-regulated which would account for the better growth of WS-FJ9 at high levels of soluble phosphate. Genes involved in glucose metabolism, including glycerate kinase, 2-oxoglutarate dehydrogenase, and sugar ABC-type transporter were continuously down-regulated which indicates that metabolic channeling of glucose towards phosphorylative pathway was negatively regulated by soluble phosphate.
2017-01-20 | GSE93761 | GEO
Project description:The aim of this study was to describe the gene expression patterns related to the differentiation and mineralization of bone-forming cells, including activation and/or repression of osteogenic or non-osteogenic pathways, remodeling of cell architecture, cell adhesion, cell communication, and assembly of extracellular matrix. The study implied patient selection, tissue collection, isolation and culture of human marrow stromal cells (hMSC) and osteoblasts (hOB), and characterization of bone-forming cells. RNA samples were collected at defined time points, in order to understand the regulation of gene expression during the processes of cell differentiation/mineralization that occur during bone repair. Transcriptome analysis was performed by using the Affymetrix GeneChip microarray technology platform and GeneChip® Human Genome U133 Plus 2.0 Array. Our results help to design a gene expression profile of bone-forming cells during specific steps of osteogenic differentiation. These findings offer an useful tool to monitor the behaviour of osteogenic precursors cultured in presence of exogenous stimuli, i.e. growth factors, or onto 3D scaffolds for bone engineering. Moreover, they can contribute to identify and clarify the role of new genes for a better understanding of the molecular mechanisms regulating osteogenesis. Experiment Overall Design: hMSC were derived from mononuclear cells (MNC) of bone marrow aspirates of four patients. MNC cultures were maintained in differentiation medium containing ascorbic acid-2 phosphate and dexamethasone, and hMSC were collected at different time points. The experimental protocol was specifically devised to mark five steps of hMSC differentiation (MD). The reference sample consisted in MNCs before the addition of differentiation medium (MD1).
2008-10-26 | E-GEOD-12265 | biostudies-arrayexpress
Project description:The response of osteoprogenitors to calcium (Ca2+) is of primary interest for both normal bone homeostasis and the clinical field of bone regeneration. The latter makes use of calcium phosphate-based bone void fillers to heal bone defects, but it is currently not known how Ca2+ released from these ceramic materials influences cells in situ. Here, we have created an in vitro environment with high extracellular Ca2+ concentration and investigated the response of human bone marrow-derived mesenchymal stromal cells (hMSCs) to it. Ca2+ enhanced proliferation and morphological changes in hMSCs. Moreover, the expression of osteogenic genes is highly increased. A 3-fold up-regulation of BMP-2 is observed after only 6 h and pharmaceutical interference with a number of proteins involved in Ca2+ sensing showed that not the calcium sensing receptor, but rather type L voltage-gated calcium channels are involved in mediating the signaling pathway between extracellular Ca2+ and BMP-2 expression. MEK1/2 activity is essential for the effect of Ca2+ and using microarray analysis, we have identified c-Fos as an early Ca2+ response gene. We have demonstrated that hMSC osteogenesis can be induced via extracellular Ca2+, a simple and economic way of priming hMSCs for bone tissue engineering applications. For more information check: https://cbit.maastrichtuniversity.nl/
2018-10-06 | E-MTAB-7222 | biostudies-arrayexpress
Project description:TAZ, a transcriptional modulator, has a key role in cell proliferation, differentiation and stem cell self-renewal. TAZ activity is regulated by several signalling pathways, including Hippo, GPCR and Wnt signalling, but the regulatory mechanisms of TAZ activation are not yet clearly understood. In this report, we show that TAZ is regulated by canonical Wnt signalling during osteogenic differentiation. Wnt3a increases TAZ expression and an inhibitor of GSK3?, a downstream effector of Wnt signalling, induces TAZ. Wnt3a facilitates the dephosphorylation of TAZ, which stabilises TAZ and prevents it from binding 14-3-3 proteins, thus inducing the nuclear localisation of TAZ. Dephosphorylation of TAZ occurs via PP1A, and depletion of PP1A blocks Wnt3a-induced TAZ stabilisation. Wnt3a-induced TAZ activates osteoblastic differentiation and siRNA-induced TAZ depletion decreases Wnt3a-induced osteoblast differentiation. Taken together, these results show that TAZ mediates Wnt3a-stimulated osteogenic differentiation through PP1A, suggesting that the Wnt signal regulates the Hippo pathway.
| S-EPMC4013522 | biostudies-literature