Caveolin-1 Plays an Important Role in the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Cardiomyocytes

Objectives: Accumulating evidence has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) may transdifferentiate into cardiomyocytes, making BMSCs a promising source of cardiomyocytes for transplantation. However, little is known about the molecular mechanisms underlying myogenic conversion of BMSCs. Methods: This study was designed to investigate the functional role of caveolin-1 in the cardiomyocyte differentiation of BMSCs and to explore the potential underlying molecular mechanisms. Results: BMSC differentiation was induced by treatment with 10 μM 5-azacytidine, and immunofluorescence assay showed that the expression of cardiomyocyte marker cardiac troponin T (cTnT) was significantly increased compared with a control group. Meanwhile, an increased caveolin-1 expression was found during the 5-azacytidine-induced BMSC differentiation. Additionally, the role of caveolin-1 in the differentiation process was then studied by using caveolin-1 siRNAs. We found that silencing caveolin-1 during induction remarkably enhanced the expression of cardiomyocyte marker genes, including cTnT, Nkx2.5 (cardiac-specific transcription factor), α-cardiac actin and α-myosin heavy chain (α-MHC). Moreover, we observed that downregulation of caveolin-1 was accompanied by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. Conclusions: Taken together, these findings demonstrate that caveolin-1 plays an important role in the differentiation of BMSCs into cardiomyocytes in conjunction with the STAT3 pathway.

Download Full-text

Dissecting Molecular Mechanisms Underlying Pulmonary Vascular Smooth Muscle Cell Dedifferentiation in Pulmonary Hypertension: Role of Mutated Caveolin-1 (Cav1F92A)-Bone Marrow Mesenchymal Stem Cells

Heart Lung and Circulation ◽

10.1016/j.hlc.2018.08.002 ◽

2019 ◽

Vol 28 (10) ◽

pp. 1587-1597 ◽

Cited By ~ 4

Author(s):

Wancheng Yu ◽

Haiying Chen ◽

Hongli Yang ◽

Jie Ding ◽

Peng Xia ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Pulmonary Hypertension ◽

Mesenchymal Stem Cells ◽

Smooth Muscle ◽

Molecular Mechanisms ◽

Cell Dedifferentiation ◽

Caveolin 1 ◽

Marrow Mesenchymal Stem Cells

Download Full-text

Effects of Severe Hypoxia on Bone Marrow Mesenchymal Stem Cells Differentiation Potential

Stem Cells International ◽

10.1155/2013/232896 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 50

Author(s):

Claudia Cicione ◽

Emma Muiños-López ◽

Tamara Hermida-Gómez ◽

Isaac Fuentes-Boquete ◽

Silvia Díaz-Prado ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Molecular Mechanisms ◽

Control Point ◽

Severe Hypoxia ◽

Marker Genes ◽

Differentiation Potential ◽

Differentiation Capacity ◽

Hypoxic Conditions

Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation capacity under normoxic and severe hypoxic culture conditions.Methods. MSCs were characterized by flow cytometry and differentiated towards adipocytes, osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The differentiations were confirmed comparing each treated point with a control point made of cells grown in DMEM and fetal bovine serum (FBS).Results. BM-MSCs from the donors displayed only few phenotypical differences in surface antigens expressions. Analyzing marker genes expression levels of the treated cells compared to their control point for each lineage showed a good differentiation in normoxic conditions and the absence of this differentiation capacity in severe hypoxic cultures.Conclusions. In our experimental conditions, severe hypoxia affects thein vitrodifferentiation potential of BM-MSCs. Adipogenic, osteogenic, and chondrogenic differentiations are absent in severe hypoxic conditions. Our work underlines that severe hypoxia slows cell differentiation by means of molecular mechanisms since a decrease in the expression of adipocyte-, osteoblast-, and chondrocyte-specific genes was observed.

Download Full-text

lncRNA NEAT1 regulates CYP1A2 and influences steroid-induced necrosis

Open Life Sciences ◽

10.1515/biol-2021-0097 ◽

2021 ◽

Vol 16 (1) ◽

pp. 969-980

Author(s):

Yongfang Zhou ◽

Fei Zhang ◽

Fengyang Xu ◽

Qiang Wang ◽

Jianhua Wu ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Control Group ◽

Marrow Mesenchymal Stem Cells ◽

Necrosis Of Femoral Head ◽

Lncrna Neat1

Abstract The main cause of steroid-induced necrosis of femoral head (SNFH) is excessive glucocorticoid (GC) intake. The aim of this article was to investigate the role of lncRNA NEAT1 as a molecular sponge to adsorb miR-23b-3p and regulate CYP1A2 in SNFH. Fluorescence in situ hybridization was used to localize lncRNA NEAT1. Human bone marrow mesenchymal stem cells (hBMSCs) were collected from patients with SNFH. The expression of lncRNA NEAT1, miR-23b-3p and CYP1A2 in hBMSCs were intervened. Compared to the control group, the lncRNA NEAT1 and CYP1A2 expression in the SNFH group was increased, while miR-23b-3p expression was decreased. GCs could inhibit the osteogenic differentiation of hBMSCs and upregulate the expression of lncRNA NEAT1. Knockdown of lncRNA NEAT1 could promote the proliferation and osteogenic differentiation of hBMSCs in the SNFH group. Overexpression of miR-23b-3p could partially counteract the effect of lncRNA NEAT1 on hBMSCs. CYP1A2 was confirmed to be a target of miR-23b-3p. Overexpression of CYP1A2 could partially rescue the effect of miR-23b-3p overexpression on hBMSCs. In conclusion, lncRNA NEAT1 as a ceRNA can adsorb miR-23b-3p and promote the expression of CYP1A2, which then inhibits the osteogenic differentiation of hBMSCs and promotes the progress of SNFH.

Download Full-text

Role of Signaling Pathways during Cardiomyocyte Differentiation of Mesenchymal Stem Cells

Cardiology ◽

10.1159/000521313 ◽

2021 ◽

Author(s):

Leila Soltani ◽

Amir Hossein Mahdavi

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Signaling Pathways ◽

Heart Development ◽

Molecular Mechanisms ◽

Adipogenic Differentiation ◽

Cardiomyocyte Differentiation ◽

Multipotent Stem Cells ◽

Promising Source

Multipotent stem cells, including mesenchymal stem cells (MSCs), represent a promising source to be used by regenerative medicine. They are capable of performing myogenic, chondrogenic, osteogenic and adipogenic differentiation. Also, MSCs are characterized by the expression of multiple surface antigens, but none of them appears to be particularly expressed on MSCs. Moreover, the prospect of monitoring and controlling MSC differentiation is a scientifically crucial regulatory and clinical requirement. Different transcription factors and signaling pathways are involved in cardiomyocyte differentiation. Due to the paucity of studies exclusively focused on cardiomyocyte differentiation of MSCs, present study aims at describing the roles of various signaling pathways (FGF, TGF, Wnt, Notch, etc.) in cardiomyocytes differentiation of MSCs. Understanding the signaling pathways that control the commitment and differentiation of cardiomyocyte cells not only will expand our basic understanding of molecular mechanisms of heart development, but also will enable us to develop therapeutic means of intervention in cardiovascular diseases.

Download Full-text

Role of bone marrow derived mesenchymal stem cells in protection of spermatogenic and Sertoli cells against histological alterations induced by torsion/detorsion in rats

Journal of Medical Histology ◽

10.21608/jmh.2017.7923 ◽

2017 ◽

Vol 1 (2) ◽

pp. 154-169

Author(s):

Samar Reda ◽

Hala Hashem ◽

Heba Elnegris ◽

Laila Elshal

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Sertoli Cells ◽

Histological Alterations

Download Full-text

MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta

Scientific Reports ◽

10.1038/s41598-021-87298-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kulisara Marupanthorn ◽

Chairat Tantrawatpan ◽

Pakpoom Kheolamai ◽

Duangrat Tantikanlayaporn ◽

Sirikul Manochantr

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Transcription Factor ◽

Osteogenic Differentiation ◽

Differentiation Potential ◽

Osteogenic Gene Expression ◽

Osteogenic Gene

AbstractMesenchymal stem cells (MSCs) are important in regenerative medicine because of their potential for multi-differentiation. Bone marrow, chorion and placenta have all been suggested as potential sources for clinical application. However, the osteogenic differentiation potential of MSCs derived from chorion or placenta is not very efficient. Bone morphogenetic protein-2 (BMP-2) plays an important role in bone development. Its effect on osteogenic augmentation has been addressed in several studies. Recent studies have also shown a relationship between miRNAs and osteogenesis. We hypothesized that miRNAs targeted to Runt-related transcription factor 2 (Runx-2), a major transcription factor of osteogenesis, are responsible for regulating the differentiation of MSCs into osteoblasts. This study examines the effect of BMP-2 on the osteogenic differentiation of MSCs isolated from chorion and placenta in comparison to bone marrow-derived MSCs and investigates the role of miRNAs in the osteogenic differentiation of MSCs from these sources. MSCs were isolated from human bone marrow, chorion and placenta. The osteogenic differentiation potential after BMP-2 treatment was examined using ALP staining, ALP activity assay, and osteogenic gene expression. Candidate miRNAs were selected and their expression levels during osteoblastic differentiation were examined using real-time RT-PCR. The role of these miRNAs in osteogenesis was investigated by transfection with specific miRNA inhibitors. The level of osteogenic differentiation was monitored after anti-miRNA treatment. MSCs isolated from chorion and placenta exhibited self-renewal capacity and multi-lineage differentiation potential similar to MSCs isolated from bone marrow. BMP-2 treated MSCs showed higher ALP levels and osteogenic gene expression compared to untreated MSCs. All investigated miRNAs (miR-31, miR-106a and miR148) were consistently downregulated during the process of osteogenic differentiation. After treatment with miRNA inhibitors, ALP activity and osteogenic gene expression increased over the time of osteogenic differentiation. BMP-2 has a positive effect on osteogenic differentiation of chorion- and placenta-derived MSCs. The inhibition of specific miRNAs enhanced the osteogenic differentiation capacity of various MSCs in culture and this strategy might be used to promote bone regeneration. However, further in vivo experiments are required to assess the validity of this approach.

Download Full-text

Role of the protease corin in chondrogenic differentiation of human bone marrow‐derived mesenchymal stem cells

Journal of Tissue Engineering and Regenerative Medicine ◽

10.1002/term.2514 ◽

2017 ◽

Vol 12 (4) ◽

pp. 973-982 ◽

Cited By ~ 3

Author(s):

Haibin Zhou ◽

Jinsong Zhu ◽

Meng Liu ◽

Qingyu Wu ◽

Ningzheng Dong

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Chondrogenic Differentiation ◽

Human Bone ◽

Human Bone Marrow

Download Full-text

Bone Marrow Mesenchymal Stem Cells (BMSCs) Transplantation Alleviates Acute Pancreatitis Through Inhibiting Inflammation and Promoting Caspase-8 Apoptosis Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2969 ◽

2022 ◽

Vol 12 (5) ◽

pp. 1034-1039

Author(s):

Xiaoxiang Wang ◽

Lan Yu ◽

Xing Xiong ◽

Yao Chen ◽

Bo Men

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Acute Pancreatitis ◽

Mesenchymal Stem Cells ◽

Serum Amylase ◽

Inflammatory Factors ◽

Control Group ◽

Caspase 8 ◽

Apoptosis Pathway ◽

Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) are capable of multipolar differentiation and repairing injured tissues. Herein, we aimed to investigate the mechanism by how BMSCs modulate the apoptotic pathway in the acute pancreatitis (AP). In this study, primary BMSCs were cultured and administrated into 10 AP mice while 10 healthy mice were taken as a blank group and 10 AP mice as a control group. The mouse pancreatic tissues were assessed by HE staining and evaluated by pancreatitis score and serum amylase detection. Level of inflammatory factors CRP and TNF-α was measured by ELISA and PIPK1, PIPK3, MLKL and Caspase-8 expression was detected by RT-qPCR and Western blot. The pancreatitis score (7.29±1.36) and the serum amylase score of (453.66±103.67) mu/ml of BMSCs group was significantly higher than that of control group, indicating increased tissue repair after BMSCs treatment. BMSCs group exhibited a higher level of CRP (711.01±115.31) and TNF-α (132.81±22.13) in serum compared to control group (p < 0.05). PIPK1, PIPK3, and MLKL expression in BMSCs group decreased (p < 0.05) whereas Caspase-8 was increased (p < 0.05). On the other hand, BMSCs group presented upregulated PIPK1, PIPK3, and MLKL (p < 0.05) and downregulated Caspase-8 (p < 0.05). In conclusion, BMSCs regulate cell apoptosis by upregulating Caspase-8 expression, and downregulating PIPK1, PIPK3 and MLKL level, thereby alleviating the inflammation in AP.

Download Full-text