scholarly journals The Phosphonate Derivative of C60 Fullerene Induces Differentiation towards the Myogenic Lineage in Human Adipose-Derived Mesenchymal Stem Cells

2021 ◽  
Vol 22 (17) ◽  
pp. 9284
Author(s):  
Svetlana V. Kostyuk ◽  
Elena V. Proskurnina ◽  
Elizaveta S. Ershova ◽  
Larisa V. Kameneva ◽  
Elena M. Malinovskaya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factors ◽  
Osteogenic Differentiation ◽  
Myogenic Differentiation ◽  
Stem Cell Differentiation ◽  
C60 Fullerene ◽  
Fullerene Derivatives ◽  
Myogenic Lineage ◽  
Differentiation Factors

Inductors of myogenic stem cell differentiation attract attention, as they can be used to treat myodystrophies and post-traumatic injuries. Functionalization of fullerenes makes it possible to obtain water-soluble derivatives with targeted biochemical activity. This study examined the effects of the phosphonate C60 fullerene derivatives on the expression of myogenic transcription factors and myogenic differentiation of human mesenchymal stem cells (MSCs). Uptake of the phosphonate C60 fullerene derivatives in human MSCs, intracellular ROS visualization, superoxide scavenging potential, and the expression of myogenic, adipogenic, and osteogenic differentiation genes were studied. The prolonged MSC incubation (within 7–14 days) with the C60 pentaphoshonate potassium salt promoted their differentiation towards the myogenic lineage. The transcription factors and gene expressions determining myogenic differentiation (MYOD1, MYOG, MYF5, and MRF4) increased, while the expression of osteogenic differentiation factors (BMP2, BMP4, RUNX2, SPP1, and OCN) and adipogenic differentiation factors (CEBPB, LPL, and AP2 (FABP4)) was reduced or did not change. The stimulation of autophagy may be one of the factors contributing to the increased expression of myogenic differentiation genes in MSCs. Autophagy may be caused by intracellular alkalosis and/or short-term intracellular oxidative stress.

Dual release of a hydrophilic and a hydrophobic osteogenic factor from a single liposome

RSC Advances ◽  
2016 ◽  
Vol 6 (115) ◽  
pp. 114599-114612 ◽  
Author(s):  
Nelson Monteiro ◽  
Albino Martins ◽  
Ricardo A. Pires ◽  
Susana Faria ◽  
Nuno A. Fonseca ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Differentiation Factors ◽  
Dual Release ◽  
Osteogenic Factor ◽  
Growth Differentiation Factors

Dual release of growth/differentiation factors from liposomes induced osteogenic differentiation of mesenchymal stem cells.

scholarly journals Effect of Sulfur on Nitrogen-Containing Plasma Polymers in Promoting Osteogenic Differentiation of Wharton’s Jelly Mesenchymal Stem Cells

2021 ◽  
Vol 50 (1) ◽  
pp. 239-251
Author(s):  
Kim Shyong Siow ◽  
Arifah Rahman ◽  
Amnani Aminuddin ◽  
Pei Yuen Ng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Osteogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Wharton’S Jelly ◽  
Oxidation States ◽  
Plasma Polymers ◽  
Wharton's Jelly ◽  
Proliferation And Differentiation

The role of sulfur and its synergistic effects with nitrogen moieties in mediating stem cell proliferation and differentiation has become of interest to the tissue engineering community due to chemical similarities with the glycosaminoglycans found in human tissues and cells. Glycosaminoglycans are biomolecules known to influence stem cell differentiation, but the roles of sulfur with different oxidation states on nitrogen-containing polymers have not been fully understood nor investigated. In this study, we used the plasma polymerization of 1,7-octadiene (ppOD), n-heptylamine (ppHA), ppHA grafted with vinyl-sulfonate via Michael-type addition (ppHA-SO3), thiophene (ppT), and ppT with air plasma treatment (ppT-air) to produce controlled amounts of nitrogen and sulfur moieties having different oxidation states, as confirmed by x-ray photoelectron spectroscopy. Assays of the proliferation and osteogenic activities of Wharton’s jelly mesenchymal stem cells (WJ-MSCs) showed the highest activities for ppHA, followed by ppHA-SO3, due to high percentages of amines/amides and the absence of SO3 moieties in ppHA. Other plasma polymers showed less proliferation and osteogenic differentiation than the positive control (glass substrate); however, WJ-MSCs grown on ppT-air with its high percentages of SO4 displayed cytoskeletons intensified with actin stress fiber, unlike the thiol-dominated ppT. Finally, the presence of methyl groups in ppOD severely limited WJ-MSCs proliferation and differentiation. Overall, these results confirm the beneficial effects of amine/amide groups on WJ-MSCs proliferation and osteogenic differentiation, but the combination of these groups with sulfur of various oxidation states failed to further enhance such cellular activities.

scholarly journals Long Non-coding RNAs LOC100126784 and POM121L9P Derived From Bone Marrow Mesenchymal Stem Cells Enhance Osteogenic Differentiation via the miR-503-5p/SORBS1 Axis

2021 ◽  
Vol 9 ◽  
Author(s):  
Yiyang Xu ◽  
Ruobing Xin ◽  
Hong Sun ◽  
Dianbo Long ◽  
Zhiwen Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Rna Binding ◽  
Expression Profiles ◽  
Stem Cell Differentiation ◽  
Luciferase Reporter ◽  
Marrow Mesenchymal Stem Cells ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) play pivotal roles in mesenchymal stem cell differentiation. However, the mechanisms by which non-coding RNA (ncRNA) networks regulate osteogenic differentiation remain unclear. Therefore, our aim was to identify RNA-associated gene and transcript expression profiles during osteogenesis in bone marrow mesenchymal stem cells (BMSCs). Using transcriptome sequencing for differentially expressed ncRNAs and mRNAs between days 0 and 21 of osteogenic differentiation of BMSCs, we found that the microRNA (miRNA) miR-503-5p was significantly downregulated. However, the putative miR-503-5p target, sorbin and SH3 domain containing 1 (SORBS1), was significantly upregulated in osteogenesis. Moreover, through lncRNA-miRNA-mRNA interaction analyses and loss- and gain-of-function experiments, we discovered that the lncRNAs LOC100126784 and POM121L9P were abundant in the cytoplasm and enhanced BMSC osteogenesis by promoting SORBS1 expression. In contrast, miR-503-5p reversed this effect. Ago2 RNA-binding protein immunoprecipitation and dual-luciferase reporter assays further validated the direct binding of miR-503-5p to LOC100126784 and POM121L9P. Furthermore, SORBS1 knockdown suppressed early osteogenic differentiation in BMSCs, and co-transfection with SORBS1 small interfering RNAs counteracted the BMSCs’ osteogenic capacity promoted by LOC100126784- and POM121L9P-overexpressing lentivirus plasmids. Thus, the present study demonstrated that the lncRNAs LOC100126784 and POM121L9P facilitate the osteogenic differentiation of BMSCs via the miR-503-5p/SORBS1 axis, providing potential therapeutic targets for treating osteoporosis and bone defects.

scholarly journals Osteogenic Response of Human Mesenchymal Stem Cells Analysed Using Combined Intracellular and Extracellular Metabolomic Monitoring

2021 ◽  
Vol 55 (3) ◽  
pp. 311-326
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Osteogenic Differentiation ◽  
Bone Microarchitecture ◽  
Human Mesenchymal Stem Cells ◽  
Stem Cell Differentiation ◽  
Extracellular Metabolite ◽  
Osteogenic Response

Background/Aims: The skeleton is a metabolically active organ undergoing continuous remodelling initiated by mesenchymal progenitors present in bone and bone marrow. Under certain pathological conditions this remodelling balance shifts towards increased resorption resulting in weaker bone microarchitecture, and there is consequently a therapeutic need to identify pathways that could inversely enhance bone formation from stem cells. Metabolomics approaches recently applied to stem cell characterisation could help identify new biochemical markers involved in osteogenic differentiation. Methods: Combined intra- and extracellular metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS) on human mesenchymal stem cells (MSCs) undergoing osteogenic differentiation in vitro. Using a combination of univariate and multivariate analyses, changes in metabolite and nutrient concentration were monitored in cultures under osteogenic treatment over 10 days. Results: A subset of differentially detected compounds was identified in differentiating cells, suggesting a direct link to metabolic processes involved in osteogenic response. Conclusion: These results highlight new metabolite candidates as potential biomarkers to monitor stem cell differentiation towards the bone lineage.

scholarly journals Dynamics of Transcription Factors in Three Early Phases of Osteogenic, Adipogenic, and Chondrogenic Differentiation Determining the Fate of Bone Marrow Mesenchymal Stem Cells in Rats

2021 ◽  
Vol 9 ◽  
Author(s):  
Qingyu Zhang ◽  
Jun Dong ◽  
Peng Zhang ◽  
Dongsheng Zhou ◽  
Fanxiao Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Transcription Factors ◽  
Osteogenic Differentiation ◽  
Chondrogenic Differentiation ◽  
Differentially Expressed ◽  
Early Responder ◽  
Marrow Mesenchymal Stem Cells ◽  
Early Phases

The imbalance of osteogenic, adipogenic, and chondrogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) occurred in multiple age-related degenerative diseases such as osteoporosis and osteoarthritis. In order to improve our understanding and control of multi-directional differentiation of BMSCs in rats, using high-throughput sequencing, we identified key gene regulatory events in the early stages of lineage commitment. Data analysis revealed two transcription factors (TFs, Tsc22d3, and Epas1) with elevated expression throughout the initiation of differentiation (3 h), lineage acquisition (12 h), and early lineage progression (72 h) of three-directional differentiation. For osteogenic differentiation, 792, 1,042, and 638 differentially expressed genes including 48, 59, and 34 TFs were identified at three time points, respectively. Moreover, the functional analysis demonstrated that 4, 12, and 5 TFs were only differentially expressed during osteogenic differentiation at 3, 12, and 72 h, respectively, and not during other two-directional differentiation. Hopx showed enhanced expression throughout three early phases during the osteogenic differentiation but no significant change in other two-directional differentiation. A similar pattern of Gbx2 expression occurred in chondrogenic differentiation. Thus, Hopx and other early responder TFs may control the osteogenic cell fate of BMSCs and participate in the development of osteoporosis. Gbx2 and other early responder TFs should be considered in mechanistic models that clarify cartilage-anabolic changes in the clinical progression of osteoarthritis.

scholarly journals Combined Effects of Mechanical Strain and Hydroxyapatite/Collagen Composite on Osteogenic Differentiation of Rat Bone Marrow Derived Mesenchymal Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Yan Huang ◽  
Xufeng Niu ◽  
Wei Song ◽  
Changdong Guan ◽  
Qingling Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Repair ◽  
Mechanical Strain ◽  
Stem Cell Differentiation ◽  
Promising Source ◽  
Rat Bone

Mesenchymal stem cells (MSCs) represent a promising source for bone repair and regeneration. Recent lines of evidence have shown that appropriate strain could regulate the osteogenic differentiation of MSCs. Our previous study demonstrated that hydroxyapatite/collagen (HA/Col) composite also played an important role in the osteogenic differentiation of MSCs. The aim of this study is to investigate the effects of mechanical strain and HA/Col composite on the osteogenic differentiation of rat bone marrow derived MSCs (rBMSCs)in vitro. rBMSCs were treated with cyclic strain generated by a self-designed stretching device with or without the presence of HA/Col composite. Osteogenic differentiation levels were evaluated using reverse transcription polymerase chain reaction (RT-PCR), alkaline phosphatase spectrophotometry, and western blotting. The results demonstrated that mechanical strain combined with HA/Col composite could obviously induce the differentiation of rBMSCs into osteoblasts, which had a better effect than only mechanical strain or HA/Col composite treatment. This provides a new avenue for mechanistic studies of stem cell differentiation and a novel approach to obtain more committed differentiated cells.

scholarly journals T-Box20 inhibits osteogenic differentiation in adipose-derived human mesenchymal stem cells: the role of T-Box20 on osteogenesis

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Samaneh Mollazadeh ◽  
Bibi Sedigheh Fazly Bazzaz ◽  
Vajiheh Neshati ◽  
Antoine A. F. de Vries ◽  
Hojjat Naderi-Meshkin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factors ◽  
Osteogenic Differentiation ◽  
Heart Development ◽  
Fluorescent Protein ◽  
Lentiviral Vector ◽  
Human Mesenchymal Stem Cells ◽  
Marker Genes ◽  
Alizarin Red

Abstract Background Skeletal development and its cellular function are regulated by various transcription factors. The T-box (Tbx) family of transcription factors have critical roles in cellular differentiation as well as heart and limbs organogenesis. These factors possess activator and/or repressor domains to modify the expression of target genes. Despite the obvious effects of Tbx20 on heart development, its impact on bone development is still unknown. Methods To investigate the consequence by forced Tbx20 expression in the osteogenic differentiation of human mesenchymal stem cells derived from adipose tissue (Ad-MSCs), these cells were transduced with a bicistronic lentiviral vector encoding Tbx20 and an enhanced green fluorescent protein. Results Tbx20 gene delivery system suppressed the osteogenic differentiation of Ad-MSCs, as indicated by reduction in alkaline phosphatase activity and Alizarin Red S staining. Consistently, reverse transcription-polymerase chain reaction analyses showed that Tbx20 gain-of-function reduced the expression levels of osteoblast marker genes in osteo-inductive Ad-MSCs cultures. Accordingly, Tbx20 negatively affected osteogenesis through modulating expression of key factors involved in this process. Conclusion The present study suggests that Tbx20 could inhibit osteogenic differentiation in adipose-derived human mesenchymal stem cells.

Design of fibronectin type III domains fused to an elastin-like polypeptide for the osteogenic differentiation of human mesenchymal stem cells

2019 ◽  
Vol 51 (8) ◽  
pp. 856-863
Author(s):  
Sujin Lee ◽  
Ji-Eun Kim ◽  
Hye-Jin Seo ◽  
Jun-Hyeog Jang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Osteogenic Differentiation ◽  
Marker Gene ◽  
Human Mesenchymal Stem Cells ◽  
Stem Cell Differentiation ◽  
Binding Motif ◽  
Type I ◽  
Type Iii

Abstract Extracellular matrix (ECM) including fibronectin (FN) and elastin plays a pivotal role in providing a microenvironment to support tissue regeneration in stem cell therapy. To develop a novel biomimetic ECM for stem cell differentiation, we engineered FN type III 9 and 10 domains fused to elastin-like polypeptides (FN-ELPs). The recombinant FN-ELP fusion protein was expressed in Escherichia coli and purified by inverse transition cycling. Human mesenchymal stem cells (hMSCs) cultured on plates coated with FN-ELP had significantly greater adhesion activity and proliferation than cells grown on non-coated plates. FN-ELP induced the osteogenic differentiation by elevating alkaline phosphatase (ALP) and mineralization activity of hMSCs. Furthermore, the osteogenic marker gene expressions of ALP, collagen type I (Col I), osteopontin (OPN), and transcriptional coactivator with a PDZ-binding motif (TAZ) were increased in hMSCs cultured on plates coated with FN-ELP. We reported a novel biomimetic ECM with potential for bone regeneration that promotes the osteogenic differentiation of hMSCs.

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