Irisin enhances chondrogenic differentiation of human mesenchymal stem cells via Rap1/PI3K/AKT axis.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE201594 | GEO | 2022/05/10
REPOSITORIES: GEO
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Project description:Irisin enhances chondrogenic differentiation of human mesenchymal stem cells via Rap1/PI3K/AKT axis.
| PRJNA832280 | ENA
Project description:A combination therapy of electromagnetic fields (EMF) and simulated microgravity (SMG) has not been examined in regenerative medicine of cartilage. In the present study, a bioreactor system using extremely low-frequency EMF and SMG was applied during the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). It was hypothesized that a beneficial effect of EMF regarding chondrogenesis (COL2A) could be combined with an avoiding effect of SMG regarding hypertrophy (COLXA1) of cartilage. Pellet cultures of hMSCs formed cartilaginous tissue under the addition of growth factors (FGF; TGF-β3). Pure SMG reduced COLXA1 expression but also COL2A expression of hMSCs. Pure EMF showed no gene expression changes of hMSCs during chondrogenic differentiation. Combining EMF/SMG resulted in a re-increase of COL2A but did not reach control levels. The COL2A to COLXA1 ratio of combined EMF/SMG was not significantly different from control levels. The combination therapy of EMF/SMG did not significantly improve the chondrogenic potential of hMSCs. chondrogenic differentiation, electromagnetic stimulation-control, 1 timepoint with/without stimulation
2015-12-31 | E-GEOD-57298 | biostudies-arrayexpress
Project description:A combination therapy of electromagnetic fields (EMF) and simulated microgravity (SMG) has not been examined in regenerative medicine of cartilage. In the present study, a bioreactor system using extremely low-frequency EMF and SMG was applied during the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). It was hypothesized that a beneficial effect of EMF regarding chondrogenesis (COL2A) could be combined with an avoiding effect of SMG regarding hypertrophy (COLXA1) of cartilage. Pellet cultures of hMSCs formed cartilaginous tissue under the addition of growth factors (FGF; TGF-β3). Pure SMG reduced COLXA1 expression but also COL2A expression of hMSCs. Pure EMF showed no gene expression changes of hMSCs during chondrogenic differentiation. Combining EMF/SMG resulted in a re-increase of COL2A but did not reach control levels. The COL2A to COLXA1 ratio of combined EMF/SMG was not significantly different from control levels. The combination therapy of EMF/SMG did not significantly improve the chondrogenic potential of hMSCs.
2015-12-31 | GSE57298 | GEO
Project description:Fibroblast growth factor-2 delays the loss of chondrogenic potential in adult bone marrow-derived mesenchymal stem cells; We compared human mesenchymal stem cells (hMSCs), expanded long-term with and without fibroblast growth factor (FGF) supplementation, with respect to their proliferation rate, and ability to differentiate along the chondrogenic pathway in vitro. hMSCs expanded in FGF-supplemented medium proliferated more rapidly than those expanded under control conditions. Aggregates of FGF-treated cells exhibited chondrogenic differentiation at passages 1 through 7, although, in some of the preparations, chondrogenic differentiation was somewhat diminished after seventh passage. Aggregates made with control cells differentiated along the chondrogenic lineage at first passage but exhibited only marginal chondrogenic differentiation after four passages and failed to form cartilage after seven passages. Microarray analysis of gene expression identified 334 transcripts that were differentially expressed in fourth passage control cells which had reduced chondrogenic potential compared to fourth passage FGF-treated cells which retained this differentiation capacity and 243 transcripts that were differentially expressed when comparing them to first passage control cells which were also capable of differentiating into chondrocytes. The intersection of these analyses yielded 49 transcripts that were differentially expressed in cells that exhibited chondrogenic differentiation in vitro compared to cells that did not. These preliminary data must now be validated to verify whether the different gene expression profiles translate into functional differences. These findings suggest that care should be exercised when extensively expanding these cells for cartilage tissue engineering applications. Experiment Overall Design: hMSCs from three different donors were expanded for up to seven passages with or without FGF supplementation. At the end of first, fourth and seventh passages the chondrogenic potential and gene expression progfiles were analyzed.
2009-11-10 | E-GEOD-14828 | biostudies-arrayexpress
Project description:Human adult mesenchymal stromal cells (hMSC) have the potential to differentiate into chondrogenic, adipogenic or osteogenic lineages, providing a potential source for tissue regeneration. An important issue for efficient bone regeneration is to identify factors that can be targeted to promote the osteogenic potential of hMSCs. Using transcriptomic analysis, we found that integrin alpha5 (ITGA5) expression is upregulated during dexamethasone-induced hMSCs osteoblast differentiation. Gain-of-function studies showed that ITGA5 promotes the expression of osteoblast phenotypic markers as well as in vitro osteogenesis in hMSCs. Downregulation of endogenous ITGA5 using shRNA blunted osteoblast marker expression and osteogenic differentiation. Pharmacological and molecular analyses showed that the enhanced hMSCs osteoblast differentiation induced by ITGA5 was mediated by activation of FAK/ERK1/2-MAPKs and PI3K signaling pathways. Remarkably, activation of ITGA5 using a specific antibody that primes the integrin or a peptide that specifically activates ITGA5 was sufficient to enhance ERK1/2-MAPKs and PI3K signaling and to promote osteoblast differentiation and osteogenic capacity of hMSCs. We also demonstrate that hMSCs engineered to over-express ITGA5 exhibited a marked increase in their osteogenic potential in vivo. These findings not only reveal that ITGA5 is required for osteoblast differentiation of adult human MSCs but also provide a novel targeted strategy using ITGA5 agonists to promote the osteogenic capacity of hMSCs, which may be used for tissue regeneration in bone disorders where the recruitment or capacity of MSCs is compromised. Experiment Overall Design: Gene expression profiles were generated from bone marrow MSC before and 1, 3 and 7 days after stimulation with 10E-7M dexamethasone to study the early molecular processes of osteogenic differentiation. 3 replicates per timepoint.
2009-09-18 | E-GEOD-18043 | biostudies-arrayexpress
Project description:Irisin, a recently identified myokine, is increased by exercise and plays pivotal roles in energy metabolism. However, it remains unknown whether irisin has any protective effects on Parkinson's disease. To examine the role of irisin in PD, irisin was peripherally delivered before or after the establishment of PD models by MPTP to explore its effect. We performed mRNA analysis in the midbrain of MPTP treated mice with irisin pre-treatment or delayed-treatment through RNA-Sequencing. And bioinformatic analysis was done on the identified deregulated genes through gene ontology (GO) analysis, KEGG pathway analysis and Gene set enrichment analysis (GSEA). Pathway analysis indicated that NAD(P)H activity and metabolism, PI3K-AKT pathway, MAPK pathway, inflammation-related signaling pathways played vital roles in the treatment of MPTP treated mice by irisin pre-treatment and irisin delayed treatment. This study provides a detailed analysis of the effects and underlying mechanisms of irisin treatment in MPTP treated mice.
2023-01-31 | GSE214542 | GEO
Project description:Long non-coding RNAs profiling of human mesenchymal stem cells comparing undifferentiated HMSCs with differentiated HMSCs during chondrogenesis. The chondrogenic differentiation of HMSCs was induced by chondrogenic medium. The chondrogenic marker genes (Col2a1, Sox9 and ACAN) has been detected upregulating during this process by Q-PCR. The aim of this study is to determine key lncRNAs regulating the chondrogenic differentiation process.
2020-03-18 | GSE128533 | GEO
Project description:Human adult mesenchymal stromal cells (hMSC) have the potential to differentiate into chondrogenic, adipogenic or osteogenic lineages, providing a potential source for tissue regeneration. An important issue for efficient bone regeneration is to identify factors that can be targeted to promote the osteogenic potential of hMSCs. Using transcriptomic analysis, we found that integrin alpha5 (ITGA5) expression is upregulated during dexamethasone-induced hMSCs osteoblast differentiation. Gain-of-function studies showed that ITGA5 promotes the expression of osteoblast phenotypic markers as well as in vitro osteogenesis in hMSCs. Downregulation of endogenous ITGA5 using shRNA blunted osteoblast marker expression and osteogenic differentiation. Pharmacological and molecular analyses showed that the enhanced hMSCs osteoblast differentiation induced by ITGA5 was mediated by activation of FAK/ERK1/2-MAPKs and PI3K signaling pathways. Remarkably, activation of ITGA5 using a specific antibody that primes the integrin or a peptide that specifically activates ITGA5 was sufficient to enhance ERK1/2-MAPKs and PI3K signaling and to promote osteoblast differentiation and osteogenic capacity of hMSCs. We also demonstrate that hMSCs engineered to over-express ITGA5 exhibited a marked increase in their osteogenic potential in vivo. These findings not only reveal that ITGA5 is required for osteoblast differentiation of adult human MSCs but also provide a novel targeted strategy using ITGA5 agonists to promote the osteogenic capacity of hMSCs, which may be used for tissue regeneration in bone disorders where the recruitment or capacity of MSCs is compromised. Keywords: Time course of osteogenic differentiation processes
2009-09-10 | GSE18043 | GEO
Project description:Fibroblast growth factor-2 delays the loss of chondrogenic potential in adult bone marrow-derived mesenchymal stem cells We compared human mesenchymal stem cells (hMSCs), expanded long-term with and without fibroblast growth factor (FGF) supplementation, with respect to their proliferation rate, and ability to differentiate along the chondrogenic pathway in vitro. hMSCs expanded in FGF-supplemented medium proliferated more rapidly than those expanded under control conditions. Aggregates of FGF-treated cells exhibited chondrogenic differentiation at passages 1 through 7, although, in some of the preparations, chondrogenic differentiation was somewhat diminished after seventh passage. Aggregates made with control cells differentiated along the chondrogenic lineage at first passage but exhibited only marginal chondrogenic differentiation after four passages and failed to form cartilage after seven passages. Microarray analysis of gene expression identified 334 transcripts that were differentially expressed in fourth passage control cells which had reduced chondrogenic potential compared to fourth passage FGF-treated cells which retained this differentiation capacity and 243 transcripts that were differentially expressed when comparing them to first passage control cells which were also capable of differentiating into chondrocytes. The intersection of these analyses yielded 49 transcripts that were differentially expressed in cells that exhibited chondrogenic differentiation in vitro compared to cells that did not. These preliminary data must now be validated to verify whether the different gene expression profiles translate into functional differences. These findings suggest that care should be exercised when extensively expanding these cells for cartilage tissue engineering applications. Keywords: time course and treatment
2009-10-29 | GSE14828 | GEO
Project description:RAP1 is well known as a telomere-binding protein; yet its functions in human stem cells remain unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by CRISPR/Cas9 and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 negatively regulated telomere length. In addition, RAP1 acted as a transcriptional regulator of RLEN by tuning the methylation status of its promoter region. Phenotypically, RAP1 deficiency resulted in enhanced self-renewal and delayed senescence in hMSCs rather than in hNSCs, suggesting a complex role of RAP1 in regulating lineage specific stem cell homeostasis. Altogether, these results indicate that RAP1 plays both telomeric and non-telomeric roles in regulating the homeostasis of human stem cells.
2018-11-20 | GSE122654 | GEO