Gene expression of TWIST1 and ZBTB16 is regulated by methylation modifications during the osteoblastic differentiation of mesenchymal stem cells

2018 ◽  
Vol 234 (5) ◽  
pp. 6230-6243 ◽  
Author(s):  
Faroogh Marofi ◽  
Ghasem Vahedi ◽  
Saeed Solali ◽  
Mohammadreza Alivand ◽  
Sadegh Salarinasab ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteoblastic Differentiation

Characterization of Mesenchymal Stem Cells Abnormalities in Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 511-511 ◽  
Author(s):  
Philippe Bourin ◽  
Jill Corre ◽  
Karène Mahtouk ◽  
Mélanie Gadelorge ◽  
Patrick Laharrague ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Plasma Cells ◽  
Osteoblastic Differentiation ◽  
Differentially Expressed ◽  
Matrix Mineralization ◽  
Protein Levels

Abstract Introduction: The bone marrow microenvironnement (BMMe) play a significant role in the physiopathology of the multiple myeloma (MM). However, its abnormality still remains controversial. To address this question, we studied bone marrow mesenchymal stem cells (MSCs), the only long-lived cells of the BMMe. We compared, at a genomic and functional level, the MSCs isolated from patients with MM, to MSCs isolated from healthy subjects and those with monoclonal gammopathy of unknown significance (MGUS). Material and methods : Bone marrow samples from 26 MM patients, 7 MGUS patients and 11 healthy individuals were compared. The MSCs were selected by their adherence on plastic and were cultured in alpha-MEM medium + 10% SVF and antibiotics during 2 passages (primo-culture = P0 and first passage = P1). The gene expression profiling was carried out by Affymetrix GeneChip microarrays (U133 plus 2.0). The expression of interesting differentially expressed genes was validated by ELISA or qRT-PCR. The phenotype was studied by flow cytometry (CD45, CD90, CD73, CD13, CD14). The CFU-F frequencies in BM samples and in cell suspensions after P0 and P1 were studied as well as the cell productions after P0 and P1. The osteoblastic differentiation was evaluated both by alkaline phosphatase dosing and matrix mineralization quantification. We also carried out co-cultures of the MSCs with CD34+ cells to quantify their hematopoietic supportive potential. Finally XG1 and Molp-6, respectively stroma independent and stroma dependent cell lines, were co-cultured with MSCs to check the capacity of the MSCs to support malignant plasma cell growth. Results: Gene expression profile independently classified the MSCs in a normal and in a MM group. MGUS MSCs were interspersed between those 2 groups. 145 distinct genes were differentially expressed in MM and normal MSCs. Among them, 46% could be involved in tumor-microenvironment cross-talk. Known soluble factors involved in MM physiopathologic features, such as IL-6, IL-1ß, DKK1 and amphiregulin, were identified and new ones found. In particular growth and differentiation factor-15 (GDF-15), already described as a accurate biomarker of numerous tumours, was significantly overexpressed (p<0.001) in MM MSCs both at mRNA and protein levels (183.5 ± 64.9 vs 749 ± 90.9 for mRNA, 1 10−4 pg/cell ± 1.9 10−5 pg/cell vs 4.3 10−4 pg/cell ± 1.4 10−4 pg/cell for protein respectively for normal and MM MSCs). It was also able to induce dose-dependant growth of Molp-6, in the absence of a supportive stroma. The phenotype and the CFU-F frequencies and the cell productions were similar in the 3 groups of MSCs and their hematopoietic supportive capacity was maintained. The MM MSCs complete differentiation towards the osteoblastic lineage, evaluated quantitatively, was faded. And very importantly, MM MSCs constituted a better supportive feeder layer for the Molp-6 cell line as compared to normal MSCs (cell expansion after 7 days : 2.1 ± 0.3 vs 3.3 ± 0.4, p = 0.04, respectively for normal and MM MSCs). On the other hand, the growth of XG1 was not influence by the subject origin of the MSCs. Conclusion: Our results show that the MSCs, like the malignant plasma cells, are abnormal in MM. This confirms the place of microenvironnement in the physiopathology of the MM and makes it possible to identify new potential therapeutic targets.

Gene expression analysis in osteoblastic differentiation from peripheral blood mesenchymal stem cells

Bone ◽  
2008 ◽  
Vol 43 (6) ◽  
pp. 1084-1092 ◽  
Author(s):  
Maria Teresa Valenti ◽  
Luca Dalle Carbonare ◽  
Luca Donatelli ◽  
Francesco Bertoldo ◽  
Mirko Zanatta ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Expression Analysis ◽  
Peripheral Blood ◽  
Gene Expression Analysis ◽  
Osteoblastic Differentiation

scholarly journals Tankyrase inhibitor XAV-939 enhances osteoblastogenesis and mineralization of human skeletal (mesenchymal) stem cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nuha Almasoud ◽  
Sarah Binhamdan ◽  
Ghaydaa Younis ◽  
Hanouf Alaskar ◽  
Amal Alotaibi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Expression Profiling ◽  
Osteoblast Differentiation ◽  
Global Gene Expression ◽  
Osteoblastic Differentiation ◽  
Global Gene Expression Profiling ◽  
Mineralized Matrix

Abstract Tankyrase is part of poly (ADP-ribose) polymerase superfamily required for numerous cellular and molecular processes. Tankyrase inhibition negatively regulates Wnt pathway. Thus, Tankyrase inhibitors have been extensively investigated for the treatment of clinical conditions associated with activated Wnt signaling such as cancer and fibrotic diseases. Moreover, Tankyrase inhibition has been recently reported to upregulate osteogenesis through the accumulation of SH3 domain-binding protein 2, an adaptor protein required for bone metabolism. In this study, we investigated the effect of Tankyrase inhibition in osteoblast differentiation of human skeletal (mesenchymal) stem cells (hMSCs). A Tankyrase inhibitor, XAV-939, identified during a functional library screening of small molecules. Alkaline phosphatase activity and Alizarin red staining were employed as markers for osteoblastic differentiation and in vitro mineralized matrix formation, respectively. Global gene expression profiling was performed using the Agilent microarray platform. XAV-939, a Tankyrase inhibitor, enhanced osteoblast differentiation of hBMSCs as evidenced by increased ALP activity, in vitro mineralized matrix formation, and upregulation of osteoblast-related gene expression. Global gene expression profiling of XAV-939-treated cells identified 847 upregulated and 614 downregulated mRNA transcripts, compared to vehicle-treated control cells. It also points towards possible changes in multiple signaling pathways, including TGFβ, insulin signaling, focal adhesion, estrogen metabolism, oxidative stress, RANK-RANKL (receptor activator of nuclear factor κB ligand) signaling, Vitamin D synthesis, IL6, and cytokines and inflammatory responses. Further bioinformatic analysis, employing Ingenuity Pathway Analysis identified significant enrichment in XAV-939-treated cells of functional categories and networks involved in TNF, NFκB, and STAT signaling. We identified a Tankyrase inhibitor (XAV-939) as a powerful enhancer of osteoblastic differentiation of hBMSC that may be useful as a therapeutic option for treating conditions associated with low bone formation.

scholarly journals JAK2 Inhibition by Fedratinib Reduces Osteoblast Differentiation and Mineralisation of Human Mesenchymal Stem Cells

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 606
Author(s):  
Nihal AlMuraikhi ◽  
Hanouf Alaskar ◽  
Sarah Binhamdan ◽  
Amal Alotaibi ◽  
Moustapha Kassem ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Osteoblastic Differentiation ◽  
Molecular Signature ◽  
Signalling Pathways ◽  
Alizarin Red ◽  
Jak2 Inhibitor

Several signalling pathways, including the JAK/STAT signalling pathway, have been identified to regulate the differentiation of human bone marrow skeletal (mesenchymal) stem cells (hBMSCs) into bone-forming osteoblasts. Members of the JAK family mediate the intracellular signalling of various of cytokines and growth factors, leading to the regulation of cell proliferation and differentiation into bone-forming osteoblastic cells. Inhibition of JAK2 leads to decoupling of its downstream mediator, STAT3, and the subsequent inhibition of JAK/STAT signalling. However, the crucial role of JAK2 in hBMSCs biology has not been studied in detail. A JAK2 inhibitor, Fedratinib, was identified during a chemical biology screen of a small molecule library for effects on the osteoblastic differentiation of hMSC-TERT cells. Alkaline phosphatase activity and staining assays were conducted as indicators of osteoblastic differentiation, while Alizarin red staining was used as an indicator of in vitro mineralised matrix formation. Changes in gene expression were assessed using quantitative real-time polymerase chain reaction. Fedratinib exerted significant inhibitory effects on the osteoblastic differentiation of hMSC-TERT cells, as demonstrated by reduced ALP activity, in vitro mineralised matrix formation and downregulation of osteoblast-related gene expression, including ALP, ON, OC, RUNX2, OPN, and COL1A1. To identify the underlying molecular mechanisms, we examined the effects of Fedratinib on a molecular signature of several target genes known to affect hMSC-TERT differentiation into osteoblasts. Fedratinib inhibited the expression of LIF, SOCS3, RRAD, NOTCH3, TNF, COMP, THBS2, and IL6, which are associated with various signalling pathways, including TGFβ signalling, insulin signalling, focal adhesion, Notch Signalling, IL-6 signalling, endochondral ossification, TNF-α, and cytokines and inflammatory response. We identified a JAK2 inhibitor (Fedratinib) as a powerful inhibitor of the osteoblastic differentiation of hMSC-TERT cells, which may be useful as a therapeutic option for treating conditions associated with ectopic bone formation or osteosclerotic metastases.

scholarly journals Modifications in Gene Expression in the Process of Osteoblastic Differentiation of Multipotent Bone Marrow-Derived Human Mesenchymal Stem Cells Induced by a Novel Osteoinductive Porous Medical-Grade 3D-Printed Poly(ε-caprolactone)/β-tricalcium Phosphate Composite

2021 ◽  
Vol 22 (20) ◽  
pp. 11216
Author(s):  
Ivan López-González ◽  
Camilo Zamora-Ledezma ◽  
María Isabel Sanchez-Lorencio ◽  
Elena Tristante Barrenechea ◽  
José Antonio Gabaldón-Hernández ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Tricalcium Phosphate ◽  
Osteoblastic Differentiation ◽  
Alizarin Red ◽  
3D Printed ◽  
Medical Grade

In this work, we evaluated the influence of a novel hybrid 3D-printed porous composite scaffold based on poly(ε-caprolactone) (PCL) and β-tricalcium phosphate (β-TCP) microparticles in the process of adhesion, proliferation, and osteoblastic differentiation of multipotent adult human bone marrow mesenchymal stem cells (ah-BM-MSCs) cultured under basal and osteogenic conditions. The in vitro biological response of ah-BM-MSCs seeded on the scaffolds was evaluated in terms of cytotoxicity, adhesion, and proliferation (AlamarBlue Assay®) after 1, 3, 7, and 14 days of culture. The osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity, mineralization (Alizarin Red Solution, ARS), expression of surface markers (CD73, CD90, and CD105), and reverse transcription–quantitative polymerase chain reaction (qRT-PCR) after 7 and 14 days of culture. The scaffolds tested were found to be bioactive and biocompatible, as demonstrated by their effects on cytotoxicity (viability) and extracellular matrix production. The mineralization and ALP assays revealed that osteogenic differentiation increased in the presence of PCL/β-TCP scaffolds. The latter was also confirmed by the gene expression levels of the proteins involved in the ossification process. Our results suggest that similar bio-inspired hybrid composite materials would be excellent candidates for osteoinductive and osteogenic medical-grade scaffolds to support cell proliferation and differentiation for tissue engineering, which warrants future in vivo research.

scholarly journals Resveratrol promotes osteogenesis of human mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1/FOXO3A axis

2011 ◽  
Vol 26 (10) ◽  
pp. 2552-2563 ◽  
Author(s):  
Pei-Chi Tseng ◽  
Sheng-Mou Hou ◽  
Ruey-Jien Chen ◽  
Hsiao-Wen Peng ◽  
Chi-Fen Hsieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells

scholarly journals Modulation of Human Mesenchymal Stem Cells by Electrical Stimulation Using an Enzymatic Biofuel Cell

Catalysts ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 62
Author(s):  
Won-Yong Jeon ◽  
Seyoung Mun ◽  
Wei Beng Ng ◽  
Keunsoo Kang ◽  
Kyudong Han ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Electrical Stimulation ◽  
Regenerative Medicine ◽  
Cell Morphology ◽  
Electrical Current ◽  
Specific Gene ◽  
Next Generation ◽  
The Impact

Enzymatic biofuel cells (EBFCs) have excellent potential as components in bioelectronic devices, especially as active biointerfaces to regulate stem cell behavior for regenerative medicine applications. However, it remains unclear to what extent EBFC-generated electrical stimulation can regulate the functional behavior of human adipose-derived mesenchymal stem cells (hAD-MSCs) at the morphological and gene expression levels. Herein, we investigated the effect of EBFC-generated electrical stimulation on hAD-MSC cell morphology and gene expression using next-generation RNA sequencing. We tested three different electrical currents, 127 ± 9, 248 ± 15, and 598 ± 75 nA/cm2, in mesenchymal stem cells. We performed transcriptome profiling to analyze the impact of EBFC-derived electrical current on gene expression using next generation sequencing (NGS). We also observed changes in cytoskeleton arrangement and analyzed gene expression that depends on the electrical stimulation. The electrical stimulation of EBFC changes cell morphology through cytoskeleton re-arrangement. In particular, the results of whole transcriptome NGS showed that specific gene clusters were up- or down-regulated depending on the magnitude of applied electrical current of EBFC. In conclusion, this study demonstrates that EBFC-generated electrical stimulation can influence the morphological and gene expression properties of stem cells; such capabilities can be useful for regenerative medicine applications such as bioelectronic devices.

Sign in / Sign up

Export Citation Format

Share Document