scholarly journals Fisetin Inhibits Osteogenic Differentiation of Mesenchymal Stem Cells via the Inhibition of YAP

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 879
Author(s):  
Chanchao Lorthongpanich ◽  
Thanapon Charoenwongpaiboon ◽  
Prapasri Supakun ◽  
Methus Klaewkla ◽  
Pakpoom Kheolamai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Cell Types ◽  
Biological Properties ◽  
Human Mscs ◽  
Protein Protein Interaction ◽  
Potential Source ◽  
Dynamics Simulations ◽  
Antioxidant Molecule

Mesenchymal stem cells (MSCs) are self-renewal and capable of differentiating to various functional cell types, including osteocytes, adipocytes, myoblasts, and chondrocytes. They are, therefore, regarded as a potential source for stem cell therapy. Fisetin is a bioactive flavonoid known as an active antioxidant molecule that has been reported to inhibit cell growth in various cell types. Fisetin was shown to play a role in regulating osteogenic differentiation in animal-derived MSCs; however, its molecular mechanism is not well understood. We, therefore, studied the effect of fisetin on the biological properties of human MSCs derived from chorion tissue and its role in human osteogenesis using MSCs and osteoblast-like cells (SaOs-2) as a model. We found that fisetin inhibited proliferation, migration, and osteogenic differentiation of MSCs as well as human SaOs-2 cells. Fisetin could reduce Yes-associated protein (YAP) activity, which results in downregulation of osteogenic genes and upregulation of fibroblast genes. Further analysis using molecular docking and molecular dynamics simulations suggests that fisetin occupied the hydrophobic TEAD pocket preventing YAP from associating with TEA domain (TEAD). This finding supports the potential application of flavonoids like fisetin as a protein–protein interaction disruptor and also suggesting an implication of fisetin in regulating human osteogenesis.

scholarly journals Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 379
Author(s):  
Rabia Ikram ◽  
Shamsul Azlin Ahmad Shamsuddin ◽  
Badrul Mohamed Jan ◽  
Muhammad Abdul Qadir ◽  
George Kenanakis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Types ◽  
Biological Properties ◽  
Research Progress ◽  
Differentiation Potential ◽  
Graphene Derivatives ◽  
Potential Applicability

Thanks to stem cells’ capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.

scholarly journals Effect of alternan versus chitosan on the biological properties of human mesenchymal stem cells

RSC Advances ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 4370-4379 ◽  
Author(s):  
Thanapon Charoenwongpaiboon ◽  
Kantpitchar Supraditaporn ◽  
Phatchanat Klaimon ◽  
Karan Wangpaiboon ◽  
Rath Pichyangkura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Biological Properties ◽  
Human Mscs

Alternan α-1,3- and α-1,6-linked glucan, promotes proliferation, migration, and differentiation of human MSCs.

scholarly journals Mesenchymal Stem Cells Isolated from Adipose and Other Tissues: Basic Biological Properties and Clinical Applications

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hakan Orbay ◽  
Morikuni Tobita ◽  
Hiroshi Mizuno
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Biological Properties ◽  
Clinical Applications ◽  
Therapeutic Tool ◽  
Adult Tissues ◽  
Clinical Benefits ◽  
Multiple Cell

Mesenchymal stem cells (MSCs) are adult stem cells that were initially isolated from bone marrow. However, subsequent research has shown that other adult tissues also contain MSCs. MSCs originate from mesenchyme, which is embryonic tissue derived from the mesoderm. These cells actively proliferate, giving rise to new cells in some tissues, but remain quiescent in others. MSCs are capable of differentiating into multiple cell types including adipocytes, chondrocytes, osteocytes, and cardiomyocytes. Isolation and induction of these cells could provide a new therapeutic tool for replacing damaged or lost adult tissues. However, the biological properties and use of stem cells in a clinical setting must be well established before significant clinical benefits are obtained. This paper summarizes data on the biological properties of MSCs and discusses current and potential clinical applications.

scholarly journals Growth on Metallo-Supramolecular Coordination Polyelectrolyte (MEPE) Stimulates Osteogenic Differentiation of Human Osteosarcoma Cells (MG63) and Human Bone Marrow Derived Mesenchymal Stem Cells

Polymers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1090 ◽  
Author(s):  
Janina Belka ◽  
Joachim Nickel ◽  
Dirk G. Kurth
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Differentiation ◽  
Osteogenic Differentiation ◽  
Three Dimensional ◽  
Cell Types ◽  
Growth Conditions ◽  
Cellular Environment ◽  
Human Osteosarcoma Cells ◽  
Supramolecular Coordination

Background: Culturing of cells is typically performed on standard tissue culture plates generating growth conditions, which in general do not reflect the native three-dimensional cellular environment. Recent investigations provide insights in parameters, which strongly affect the general cellular behavior triggering essential processes such as cell differentiation. The physical properties of the used material, such as stiffness, roughness, or topology, as well as the chemical composition of the cell-surface interface are shown to play a key role in the initiation of particular cellular responses. Methods: We extended our previous research, which identified thin films of metallo-supramolecular coordination polyelectrolytes (MEPEs) as substrate to trigger the differentiation of muscular precursor cells. Results: Here, we show that the same MEPEs similarly stimulate the osteogenic differentiation of pre-osteoblasts. Remarkably, MEPE modified surfaces also trigger the differentiation of primary bone derived mesenchymal stem cells (BMSCs) towards the osteogenic lineage. Conclusion: This result leads to the conclusion that these surfaces individually support the specification of cell differentiation toward lineages that correspond to the natural commitment of the particular cell types. We, therefore, propose that Fe-MEPEs may be used as scaffold for the treatment of defects at least in muscular or bone tissue.

scholarly journals Myocilin Stimulates Osteogenic Differentiation of Mesenchymal Stem Cells through Mitogen-activated Protein Kinase Signaling

2013 ◽  
Vol 288 (23) ◽  
pp. 16882-16894 ◽  
Author(s):  
Heung Sun Kwon ◽  
Thomas V. Johnson ◽  
Stanislav I. Tomarev
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Open Angle Glaucoma ◽  
Mitogen Activated Protein Kinase ◽  
Human Mscs ◽  
Kinase Signaling ◽  
Wild Type

Myocilin is a secreted glycoprotein that is expressed in ocular and non-ocular tissues. Mutations in the MYOCILIN gene may lead to juvenile- and adult-onset primary open-angle glaucoma. Here we report that myocilin is expressed in bone marrow-derived mesenchymal stem cells (MSCs) and plays a role in their differentiation into osteoblasts in vitro and in osteogenesis in vivo. Expression of myocilin was detected in MSCs derived from mouse, rat, and human bone marrow, with human MSCs exhibiting the highest level of myocilin expression. Expression of myocilin rose during the course of human MSC differentiation into osteoblasts but not into adipocytes, and treatment with exogenous myocilin further enhanced osteogenesis. MSCs derived from Myoc-null mice had a reduced ability to differentiate into the osteoblastic lineage, which was partially rescued by exogenous extracellular myocilin treatment. Myocilin also stimulated osteogenic differentiation of wild-type MSCs, which was associated with activation of the p38, Erk1/2, and JNK MAP kinase signaling pathways as well as up-regulated expression of the osteogenic transcription factors Runx2 and Dlx5. Finally, cortical bone thickness and trabecular volume, as well as the expression level of osteopontin, a known factor of bone remodeling and osteoblast differentiation, were reduced dramatically in the femurs of Myoc-null mice compared with wild-type mice. These data suggest that myocilin should be considered as a target for improving the bone regenerative potential of MSCs and may identify a new role for myocilin in bone formation and/or maintenance in vivo.

scholarly journals SIRT1 Inhibition Affects Angiogenic Properties of Human MSCs

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Botti Chiara ◽  
Caiafa Ilaria ◽  
Coppola Antonietta ◽  
Cuomo Francesca ◽  
Miceli Marco ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Therapeutic Angiogenesis ◽  
Induced Response ◽  
Human Mscs ◽  
Hypoxic Conditions ◽  
And Migration

Human mesenchymal stem cells (hMSCs) are attractive for clinical and experimental purposes due to their capability of self-renewal and of differentiating into several cell types. Autologous hMSCs transplantation has been proven to induce therapeutic angiogenesis in ischemic disorders. However, the molecular mechanisms underlying these effects remain unclear. A recent report has connected MSCs multipotency to sirtuin families, showing that SIRT1 can regulate MSCs function. Furthermore, SIRT1 is a critical modulator of endothelial angiogenic functions. Here, we described the generation of an immortalized human mesenchymal bone marrow-derived cell line and we investigated the angiogenic phenotype of our cellular model by inhibiting SIRT1 by both the genetic and pharmacological level. We first assessed the expression of SIRT1 in hMSCs under basal and hypoxic conditions at both RNA and protein level. Inhibition of SIRT1 by sirtinol, a cell-permeable inhibitor, or by specific sh-RNA resulted in an increase of premature-senescence phenotype, a reduction of proliferation rate with increased apoptosis. Furthermore, we observed a consistent reduction of tubule-like formation and migration and we found that SIRT1 inhibition reduced the hypoxia induced accumulation of HIF-1α protein and its transcriptional activity in hMSCs. Our findings identify SIRT1 as regulator of hypoxia-induced response in hMSCs and may contribute to the development of new therapeutic strategies to improve regenerative properties of mesenchymal stem cells in ischemic disorders through SIRT1 modulation.

scholarly journals Four and a Half LIM Domains Protein 2 Mediates Bortezomib-Induced Osteogenic Differentiation of Mesenchymal Stem Cells in Multiple Myeloma Through p53 Signaling and β-Catenin Nuclear Enrichment

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhenqing Xie ◽  
Yan Xu ◽  
Xiaojing Wei ◽  
Gang An ◽  
Mu Hao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Bone Disease ◽  
Marker Genes ◽  
Human Mscs ◽  
P53 Signaling ◽  
Lim Domains

Myeloma bone disease (MBD), caused by the inhibition of osteoblast activity and the activation of osteoclast in the bone marrow environment, is the most frequent and life-threatening complication in multiple myeloma (MM) patients. Bortezomib (Bzb) was shown to promote MM-derived mesenchymal stem cells (MM-MSCs) differentiation to osteoblast in vitro and in animal models, promoting the bone formation and regeneration, may be mediated via β-catenin/T-cell factor (TCF) pathway. Further defining molecular mechanism of Bzb-enhanced bone formation in MM will be beneficial for the treatment of myeloma patients. The present study has identified for the first time four and a half LIM domains protein 2 (FHL2), a tissue-specific coregulator that interacts with many osteogenic marker molecules, as a therapeutic target to ameliorate MM bone disease. First, increased messenger RNA (mRNA) and protein levels of FHL2, and the mRNA level of main osteoblast markers (including Runx2, ALP, and Col1A1), were found in MM-patients-derived MSCs after Bzb treatment. FHL2 KD with short hairpin RNA (shRNA) reduced the expression of osteoblast marker genes and blocked the osteogenic differentiation of MM-MSCs regardless of the presence or absence of Bzb, implying that FHL2 is an important activator of the osteogenic differentiation of human MSCs under a proteasome inhibition condition. Molecular analysis showed that the enhanced expression of FHL2 was associated with the Bzb-induced upregulation of p53. No significant change at protein level of total β-catenin was observed with or without Bzb treatment. However, it was mostly enriched to nuclei in MSCs after Bzb treatment. Moreover, β-catenin was restricted to the perinuclear region in FHL2 KD cells. These data provide evidence that FHL2 is essential for promoting β-catenin nuclear enrichment in MM-MSCs. In conclusion, FHL2 is critical for Bzb-induced osteoblast differentiation of MM-MSCs and promotes the osteogenesis, through p53 signaling and β-catenin activation. Targeting FHL2 in MM may provide a new therapeutic strategy for treating MBD.

scholarly journals Culture of rat mesenchymal stem cells on PHBV-PCL scaffolds: analysis of conditioned culture medium by FT-Raman spectroscopy

2023 ◽  
Vol 83 ◽  
Author(s):  
V. A. Nascimento ◽  
S. M. Malmonge ◽  
A. R. Santos Jr.
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Raman Spectroscopy ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Functional Groups ◽  
Culture Media ◽  
Cell Types ◽  
Ft Raman Spectroscopy ◽  
Ft Raman

Abstract Mesenchymal stem cells (MSCs) have great potential for application in cell therapy and tissue engineering procedures because of their plasticity and capacity to differentiate into different cell types. Given the widespread use of MSCs, it is necessary to better understand some properties related to osteogenic differentiation, particularly those linked to biomaterials used in tissue engineering. The aim of this study was to develop an analysis method using FT-Raman spectroscopy for the identification and quantification of biochemical components present in conditioned culture media derived from MSCs with or without induction of osteogenic differentiation. All experiments were performed between passages 3 and 5. For this analysis, MSCs were cultured on scaffolds composed of bioresorbable poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) polymers. MSCs (GIBCO®) were inoculated onto the pure polymers and 75:25 PHBV/PCL blend (dense and porous samples). The plate itself was used as control. The cells were maintained in DMEM (with low glucose) containing GlutaMAX® and 10% FBS at 37oC with 5% CO2 for 21 days. The conditioned culture media were collected and analyzed to probe for functional groups, as well as possible molecular variations associated with cell differentiation and metabolism. The method permitted to identify functional groups of specific molecules in the conditioned medium such as cholesterol, phosphatidylinositol, triglycerides, beta-subunit polypeptides, amide regions and hydrogen bonds of proteins, in addition to DNA expression. In the present study, FT-Raman spectroscopy exhibited limited resolution since different molecules can express similar or even the same stretching vibrations, a fact that makes analysis difficult. There were no variations in the readings between the samples studied. In conclusion, FT-Raman spectroscopy did not meet expectations under the conditions studied.

scholarly journals MicroRNAs Regulation in Osteogenic Differentiation of Mesenchymal Stem Cells

2021 ◽  
Vol 2 ◽  
Author(s):  
Xiao Han ◽  
Zhipeng Fan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Pluripotent Stem Cell ◽  
Target Genes ◽  
Cell Types ◽  
Clinical Applications ◽  
Self Renewal ◽  
Epigenetic Factor ◽  
Osteogenic Property

Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cell with the potential of self-renewal and multidirectional differentiation. They can be obtained from a variety of tissues and can differentiate into a variety of cell types under different induction conditions, including osteoblasts. Because of this osteogenic property, MSCs have attracted much attention in the treatment of bone metabolism-related diseases. MicroRNAs (miRNAs), as an epigenetic factor, are thought to play an important regulatory role in the process of osteogenic differentiation of MSCs. In recent years, increasingly evidence shows that miRNAs imbalance is involved in the regulation of osteoporosis and fracture. In this review, miRNAs involved in osteogenic differentiation and their mechanisms for regulating the expression of target genes are reviewed. In addition, we also discuss the potential clinical applications and possible directions of this field in the future.

314 ADIPOSE- AND BONE MARROW-DERIVED MESENCHYMAL STEM CELLS PRESENT LARGE SIMILARITIES IN TRANSCRIPTOME PRIOR TO AND DURING ADIPOGENIC AND OSTEOGENIC DIFFERENTIATION

2011 ◽  
Vol 23 (1) ◽  
pp. 253 ◽  
Author(s):  
E. Monaco ◽  
M. Bionaz ◽  
A. Lima ◽  
W. L. Hurley ◽  
M. B. Wheeler
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Antigen Presentation ◽  
Osteogenic Differentiation ◽  
Adipogenic Differentiation ◽  
Cell Types ◽  
Significant Enrichment ◽  
Post Hoc

Previous data support adipose-derived stem cells as an alternative to bone marrow as a source of adult stem cells for therapeutic purposes. The aim of the present study was to directly compare the transcriptome of adipose-derived (ADSC) and bone marrow-derived (BMSC) mesenchymal stem cells prior to differentiation and during in vitro osteogenic and adipogenic differentiation. The ADSC and BMSC were harvested from 3 adult pigs and differentiated in vitro into adipocytes and osteocytes for up to 4 weeks. Prior to differentiation and at differentiation day 2, 7, and 21, cells were harvested and RNA extracted for transcriptomics analysis by a 13 263 oligo 70-mers array (Sus scrofa AROS V1.0 with extension; Operon). Data were normalized by Lowess and statistical analysis was run using ANOVA with Benjamini-Hochberg false discovery rate (FDR) correction. Data mining was carried out using Ingenuity Pathway Analysis and David. Using an FDR of <0.05 for overall tissue effect and a post-hoc correction of P < 0.001, we observed 65 differentially expressed genes (DEG) between ADSC and BMSC before starting differentiation (0.66% of unique genes in the array). Functional analysis uncovered significant enrichment of extracellular matrix genes with direct roles in cell adhesion, migration, movement, and morphology. When the interaction cell type × differentiation × time was assessed, we observed >2 000 DEG with an FDR <0.05. This large number was mostly due to time effects. When pair-wise comparisons between cell types for each time point during the same differentiation were performed (post-hoc P < 0.001), we observed a strikingly low number of DEG. The number of DEG was lower between cell types in osteogenic (<100 DEG) compared with adipogenic (<200 DEG) differentiation. We observed significant enrichment (FDR-corrected P-value cut-off <0.05) of functions related to metabolism, antigen presentation, angiogenesis, and cell cycle in both differentiation conditions. We also observed an overall greater induction of the enriched functions in ADSC and a decrease in BMSC during adipogenic differentiation and the opposite during osteogenic differentiation except for metabolism, which appeared to be larger in ADSC in all cases. Among the significant enriched functions of DEG between the 2 differentiations, we observed enrichment of genes involved in metabolism, cell death, cell-to-cell signalling, and antigen presentation in ADSC during adipogenic compared with osteogenic differentiation. In BMSC we observed enrichment of functions related to cell death, antigen presentation, and lipid metabolism in osteogenic v. adipogenic differentiation. Overall data uncovered a high similarity at the transcriptional level between ADSC and BMSC both prior to differentiation and during differentiation. Those data support ADSC being particularly similar to BMSC. This work was support by the Illinois Regenerative Medicine Institute (IDPH # 63080017).

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