Activation of transcriptional factor ZBTB16 expression during osteogenic differentiation of mesenchymal stem cells

Aim. Calcified aortic valve stenosis is the third leading cause of cardiovascular disease. The mechanisms underlying this process remain unclear, however, it is known that they are largely similar to the formation of bone tissue during embryonic development, as well as in the postnatal period during regeneration. There is evidence for the involvement of Zinc Finger and BTB Domain Containing 16 (ZBTB16) in skeletal development. At the same time, a number of studies carried out on different types of cell cultures indicate a contradictory and ambiguous effect of ZBTB16 on RUNX2 expression. Thus, the aim of this study was to investigate the dynamic variability of ZBTB16 expression, as well as its role in aortic valve calcification.Methods. The study used different types of mesenchymal cells cultures - aortic valve interstitial cells, umbilical cord mesenchymal stem cells, ligament stem cells and dental pulp stem cells. Changes in ZBTB16 and RUNX2 expression levels under the influence of osteogenic stimuli, as well as during exogenous activation of ZBTB16, were analyzed using real-time PCR. Expression levels of some osteogenic markers - BMP2,4, COL1A1, IBSP, DLX2, PDK4 - were analyzed in the interstitial cells of the aortic valve.Results. The results of the study indicate that a significant increase in the expression of ZBTB16 is observed during the induction of osteogenic differentiation of various cell cultures - interstitial cells of the aortic valve, mesenchymal stem cells of the umbilical cord, stem cells of the ligaments and dental pulp. Apparently, the processes of osteogenic differentiation of aortic valve interstitial cells, in the presence of dexamethasone in cultivation medium, are provided through RUNX2-dependent signaling for the further activation of osteogenic markers.Conclusion. The study of modulation of cellular signals by ZBTB16, when activating or suppressing the work of a transcriptional factor, in the future may bring us closer to the ability to enhance the regenerative abilities of bone tissue cells or, conversely, prevent calcification of the aortic valve tissues.

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Collagen synthesis by mesenchymal stem cells and aortic valve interstitial cells in response to mechanical stretch

Cardiovascular Research ◽

10.1016/j.cardiores.2006.03.022 ◽

2006 ◽

Vol 71 (3) ◽

pp. 548-556 ◽

Cited By ~ 111

Author(s):

C KU ◽

P JOHNSON ◽

P BATTEN ◽

P SARATHCHANDRA ◽

R CHAMBERS ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Aortic Valve ◽

Collagen Synthesis ◽

Mechanical Stretch ◽

Interstitial Cells ◽

Valve Interstitial Cells

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miRNA-126 Inhibits Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells (BMSCs)

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2943 ◽

2022 ◽

Vol 12 (4) ◽

pp. 794-799

Author(s):

Le Chang ◽

Wei Duan ◽

Chuang Wang ◽

Jian Zhang

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Mrna Level ◽

Alizarin Red ◽

Runx2 Expression ◽

Alp Activity ◽

Smad4 Protein ◽

Marrow Mesenchymal Stem Cells

This study was to determine whether microRNA (miRNA)-126 regulates osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Rat BMSCs were extracted and stimulated for osteogenic differentiation. Functional experiments were conducted to assess miR-126’s impact on BMSCs differentiation. Western blot and RT-qPCR determined miR-126 expression. ALP activity detection and alizarin red staining detection were also performed. After osteogenic differentiation of BMSCs, miR-126 expression was gradually decreased over time. Overexpression of miR-26 decreased ALP activity, Notch signaling activity as well as declined Runx2 expression and calcium Salt nodules after treatment. Importantly, we found that Smad4 serves as a target of miR-126 while upregulation of the miRNA was accompanied with the decreased Smad4 protein expression without affecting the Smad4 mRNA level. In conclusion, miR-126 restrains osteogenic differentiation through inhibition of SMAD4 signaling, providing a novel insight into the mechanism.

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Proteo-transcriptomic analysis of osteogenic differentiation of valve interstitial cells from patients with calcific aortic valve disease

Bone Reports ◽

10.1016/j.bonr.2020.100303 ◽

2020 ◽

Vol 13 ◽

pp. 100303

Author(s):

Arseniy Lobov ◽

Daria Semenova ◽

Aleksandra Kostina ◽

Artem Kiselev ◽

Arsenii Zabirnyk ◽

...

Keyword(s):

Aortic Valve ◽

Osteogenic Differentiation ◽

Aortic Valve Disease ◽

Interstitial Cells ◽

Transcriptomic Analysis ◽

Valve Disease ◽

Calcific Aortic Valve Disease ◽

Valve Interstitial Cells

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Exosome-Derived miR21/SMAD7 Derived from Donor Osteoporosis Mesenchymal Stem Cells Inhibits Osteogenic Differentiation of Reconstituted Hosts

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2019.2154 ◽

2019 ◽

Vol 9 (10) ◽

pp. 1346-1354

Author(s):

Jie Chen ◽

Yongsheng Luo ◽

Ting Li ◽

Wenbo Yang ◽

Wen Zhang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Runx2 Expression ◽

Alp Activity ◽

Marrow Mesenchymal Stem Cells ◽

Smad7 Expression ◽

Different Sources ◽

Adult Mscs ◽

Normal Adults

Exogenous bone marrow mesenchymal stem cells (MSCs) can regulate osteogenic differentiation. MicroRNA-21 has been shown to target SMAD7. This study explored the mechanism by which miR-21/SMAD7 inhibits osteogenic differentiation from exosomes secreted by osteoporosis patients-derived MSCs. Exosomes were obtained from MSCs and miR-21 expression was detected. Normal MSCs were treated with exosomes secreted by MSCs from different sources for osteogenic differentiation followed by detection of ALP, Bglap and Runx2 level and ALP activity. Normal MSCs were divided into three groups, which were treated with exosomes from normal adult MSCs, osteoporosis patients-derived MSCs and osteoporosis patients-derived MSCs + SMAD7 overexpression followed by analysis of the mRNA expression of ALP, Bglap and Runx2 by qRT-PCR and ALP activity. miR-21 expression in exosomes from osteoporosis patients-derived MSCs was significantly higher than that from normal adults MSCs. After treatment with exosomes from osteoporosis patients-derived MSCs, Runx2 expression and ALP activity was significantly decreased. SMAD7 expression in osteoporosis patients was significantly lower than that in normal adults. The expression of ALP, Bglap and Runx2 is significantly decreased after overexpression of SMAD7. SMAD7 is a target gene of miR-21 and plays a role in inhibiting osteogenic differentiation induced by exosomes from osteoporosis-derived MSCs.

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miRNA Expression Profiling Uncovers a Role of miR-139-5p in Regulating the Calcification of Human Aortic Valve Interstitial Cells

Frontiers in Genetics ◽

10.3389/fgene.2021.722564 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fan Zhang ◽

Naixuan Cheng ◽

Yingchun Han ◽

Congcong Zhang ◽

Haibo Zhang

Keyword(s):

Aortic Valve ◽

Osteogenic Differentiation ◽

Mirna Expression ◽

Structural Heart Disease ◽

Interstitial Cells ◽

Calcific Aortic Valve Disease ◽

Valve Interstitial Cells ◽

Functional Studies ◽

Human Aortic Valve ◽

Osteogenic Gene

Calcific aortic valve disease (CAVD) is the most common structural heart disease, and the morbidity is increased with elderly population. Several microRNAs (miRNAs) have been identified to play crucial roles in CAVD, and numerous miRNAs are still waiting to be explored. In this study, the miRNA expression signature in CAVD was analyzed unbiasedly by miRNA-sequencing, and we found that, compared with the normal control valves, 152 miRNAs were upregulated and 186 miRNAs were downregulated in calcified aortic valves. The functions of these differentially expressed miRNAs were associated with cell differentiation, apoptosis, adhesion and immune response processes. Among downregulated miRNAs, the expression level of miR-139-5p was negatively correlated with the osteogenic gene RUNX2, and miR-139-5p was also downregulated during the osteogenic differentiation of primary human aortic valve interstitial cells (VICs). Subsequent functional studies revealed that miR-139-5p overexpression inhibited the osteogenic differentiation of VICs by negatively modulating the expression of pro-osteogenic gene FZD4 and CTNNB1. In conclusion, these results suggest that miR-139-5p plays an important role in osteogenic differentiation of VICs via the Wnt/β-Catenin pathway, which may further provide a new therapeutic target for CAVD.

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Osteogenic differentiation of human gingival mesenchymal stem cells byAristolochia bracteolatasupplementation through enhanced Runx2 expression

Journal of Cellular Physiology ◽

10.1002/jcp.25835 ◽

2017 ◽

Vol 232 (7) ◽

pp. 1591-1595 ◽

Cited By ~ 5

Author(s):

Dinesh Murugan Girija ◽

Suresh Y Ranga Rao ◽

Mangathayaru Kalachaveedu ◽

Rajasekaran Subbarayan

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Runx2 Expression

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Adenosine A1 receptor stimulation enhances osteogenic differentiation of human dental pulp-derived mesenchymal stem cells via WNT signaling

Stem Cell Research ◽

10.1016/j.scr.2013.04.002 ◽

2013 ◽

Vol 11 (1) ◽

pp. 611-624 ◽

Cited By ~ 27

Author(s):

Iolanda D'Alimonte ◽

Eleonora Nargi ◽

Angela Lannutti ◽

Marco Marchisio ◽

Laura Pierdomenico ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Wnt Signaling ◽

Osteogenic Differentiation ◽

Dental Pulp ◽

Adenosine A1 Receptor ◽

Receptor Stimulation ◽

Adenosine A1 ◽

Human Dental Pulp ◽

A1 Receptor

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ID:2050 Impacts of polymer-based and graphene-based biomaterials on the characteristics of Wharton jelly’s-derived mesenchymal stem cells

Biomedical Research and Therapy ◽

10.15419/bmrat.v4is.284 ◽

2017 ◽

Vol 4 (S) ◽

pp. 80

Author(s):

Hiew Vun Vun

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Molecular Mechanisms ◽

Surface Markers ◽

Rt Pcr ◽

Alizarin Red ◽

Runx2 Expression ◽

Gene Profiles ◽

Different Types ◽

Different Characteristics

The combination of mesenchymal stem cells (MSCs) and biomaterials scaffolds hold significant promise in tissue engineering and regenerative medicine field. In recent years, expansion and differentiation of MSCs culturing with polymer-based and graphene-based biomaterials have been intensely studied. However, the underlying molecular mechanisms are still largely unknown. This study was to examine the different characteristics of Wharton’s jelly (WJ)-derived MSCs using two different types of biomaterials including polymer-based (PU157) and graphene oxide-based (GO). In term of proliferation, WJ-MSCs culturing with PU157 and GO showed no significant differences compared to the controls. PU157 and GO had no effects on morphological features of WJ-MSCs. RT-PCR results showed that all WJ-MSCs co-culturing with or without PU157 and GO expressed positive surface markers including CD29, CD44, CD73, CD90, CD105, CD106 and CD166 but the expression of negative markers (CD34, CD45 and CD133) was undetectable. The SOX2 and RUNX2 expression were both upregulated in WJ-MSCs combining with PU157 when compared to the controls at passage 6, where no obvious difference was observed in passage 3. Interestingly, COL2A expression became more noticeable in the presence of PU157 at passage 6 than passage 3. In contrast, GO did not alter the expression of stemness, osteogenic, adipogenic and chondrogenic genes. Both alizarin red and oil red staining showed calcium and lipid deposition in WJ-MSCs co-cultured with PU157 and GO respectively, suggesting the presence of osteoblast- and adipocyte-like cells. In conclusion, PU157 exerted certain effects on the expression gene profiles at later passage and able to enhance differentiation abilities in WJ-MSCs.

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