scholarly journals Mechano growth factor E peptide regulates migration and differentiation of bone marrow mesenchymal stem cells

2013 ◽  
Vol 52 (2) ◽  
pp. 111-120 ◽  
Author(s):  
Hanwei Cui ◽  
Qian Yi ◽  
Jianguo Feng ◽  
Li Yang ◽  
Liling Tang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Adipogenic Differentiation ◽  
Expression Levels ◽  
Migration Effect ◽  
Mechano Growth Factor ◽  
Marrow Mesenchymal Stem Cells ◽  
Igf1 Receptor

IGF1Ec in humans or IGF1Eb in rodents (known as mechano growth factor (MGF)) has a unique E domain, and the C-terminal end of the E domain (MGF E peptide) plays important roles in proliferation, migration and differentiation of many cell types. Bone marrow mesenchymal stem cells (BMSCs) have multiple differentiation potentials and are considered as perfect seed cells for tissue repair. But the role of MGF E peptide on BMSCs is seldom investigated and the mechanism is still unclear. In this study, we investigated the effects of MGF E peptide on rat BMSCs (rBMSCs). Our results revealed that treatment with MGF E peptide had no effect on BMSC proliferation. However, both wound-healing and transwell assays indicated that MGF E peptide could significantly enhance rBMSCs migration ability. Further analysis indicated that MGF E peptide also reduced the expression levels of osteogenic genes, but increased the expression levels of adipogenic genes. Analysis of molecular mechanism showed that phosphorylation-Erk1/2 was activated by MGF E peptide and blockage of either Erk1/2 or IGF1 receptor could repress the migration effect of MGF E peptide. In conclusion, MGF E peptide is able to inhibit osteogenic differentiation but promote adipogenic differentiation. In addition, the migration effect of MGF E peptide on rBMSCs depends on IGF1 receptor via Erk1/2 signal pathway.

scholarly journals The BMP signaling pathway enhances the osteoblastic differentiation of bone marrow mesenchymal stem cells in rats with osteoporosis

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Bin Zhao ◽  
Gengyan Xing ◽  
Aiyuan Wang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Adipogenic Differentiation ◽  
Osteoblastic Differentiation ◽  
Bmp Signaling ◽  
Blank Group ◽  
Expression Levels ◽  
Marrow Mesenchymal Stem Cells

Abstract Background This study was conducted with the aim of exploring the effect of the BMP signaling pathway on osteoblastic differentiation in rat bone marrow mesenchymal stem cells (rBMSCs) in rats with osteoporosis (OP). Methods The bilateral ovaries of female SD rats were resected for the establishment of a rat OP model. The osteoblastic differentiation of isolated rBMSCs was identified through osteogenic induction. Adipogenetic induction and flow cytometry (FCM) were used to detect adipogenic differentiation and the expression of rBMSC surface markers. The rBMSCs were grouped into the blank group, NC group, si-BMP2 group, and oe-BMP2 group. The expression levels of key factors and osteogenesis-related factors were determined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The formation of calcified nodules was observed by alizarin red staining. ALP activity was measured by alkaline phosphatase staining. Results The rats with OP had greater weight but decreased bone mineral density (BMD) than normal rats (all P < 0.01). The rBMSCs from rats with OP were capable of osteoblastic differentiation and adipogenic differentiation and showed high expression of CD44 (91.3 ± 2.9%) and CD105 (94.8 ± 2.1%). Compared with the blank group, the oe-BMP2 group had elevated BMP-2 and Smad1 levels and an increase in calcified nodules and ALP-positive staining areas (all P < 0.05). Moreover, the expression levels of Runx2, OC, and OPN in the oe-BMP2 group were relatively higher than those in the blank group (all P < 0.05). The findings in the si-BMP2 group were opposite to those in the oe-BMP2 group. Conclusion BMP signaling pathways activated by BMP-2 can promote the osteoblastic differentiation of rBMSCs from rats with OP.

scholarly journals The involvement of mitochondrial fission in maintenance of the stemness of bone marrow mesenchymal stem cells

2019 ◽  
Vol 244 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Xiaorong Feng ◽  
Wenjing Zhang ◽  
Wen Yin ◽  
Y James Kang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Protein Level ◽  
Mitochondrial Dynamics ◽  
Adipogenic Differentiation ◽  
Mitochondrial Fission ◽  
Mitochondrial Fusion ◽  
Marrow Mesenchymal Stem Cells

Mitochondrial dynamics, a complicated cellular process consisting of mitochondrial fusion and fission, has been suggested to be involved in regulating the stemness of bone marrow mesenchymal stem cells (BMSCs). This study was undertaken to explore the relationship between mitochondrial dynamics and the maintenance of BMSCs’ stemness. Rat BMSCs were treated with fibroblast growth factor 2 (FGF2) and epithelial growth factor (EGF) to induce differentiation. Mitochondrial dynamics was determined by mitochondrial length observed by confocal microscope and DLP1 (a protein promoting mitochondrial fission), OPA1 (a protein promoting mitochondrial fusion) expression revealed by Western blotting analysis. BMSCs’ stemness was determined by flow cytometry and osteogenic/adipogenic differentiation ability. We found that in the process of BMSCs differentiation, mitochondrial length was increased, along with a decreased protein level of DLP1 and an increased protein level of OPA1 in the mitochondria, indicating a shift toward mitochondrial fusion in BMSCs during differentiation. Notably, when the mitochondrial fission was inhibited by Mdivi-1, the stemness marker, CD90, was deceased along with the reduction of DLP1 expression. Under the same condition, the potential of BMSCs to be induced into adipocytes or osteocytes was decreased. Correspondingly, when BMSCs were treated with tyrphostin A9, a reagent promoting mitochondrial fission by increasing DLP1, the stemness marker, CD54, was increased with an increased potential of BMSCs to be induced into adipocytes or osteocytes. Hence, our results demonstrated that mitochondrial fission contributed to the maintenance of BMSCs’ stemness. Impact statement How to maintain the stemness of bone marrow mesenchymal stem cells (BMSCs) in cultures is a long-standing question. The present study found that mitochondrial dynamics affects the stemness of BMSCs in cultures and the retaining of mitochondrial fission enhances the stemness of BMSCs. This work thus provides a novel insight into strategic approaches to maintain the stemness of BMSCs in cultures in relation to the clinical application of bone-marrow stem cells.

Effect of Sirtuin1 (Sirt1) on Bone Marrow Mesenchymal Stem Cells (BMSCs) Osteogenesis/Adipogenesis via β-Catenin/The Transcription Factor T Cell Factor 1 (TCF1)/Runt-Related Transcription Factor 2 (RUNX2)

2021 ◽  
Vol 11 (10) ◽  
pp. 2070-2075
Author(s):  
Wenji Shi ◽  
Mingxing Zhao ◽  
Guangxia Shi
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Sham Operation ◽  
Runx2 Expression ◽  
Sham Operation Group ◽  
Marrow Mesenchymal Stem Cells ◽  
Operation Group ◽  
Sirna Group

Bone marrow mesenchymal stem cells (BMSCs) have self-renewal potential. Sirt1 regulates cell differentiation and apoptosis. However, Sirt1’s effect on BMSCs osteogenic/adipogenic differentiation has not been fully elucidated. SD rats were randomly divided into Osteoporosis (OP) group and sham operation group. OP rat BMSCs were isolated and assigned into control group, NC group and Sirt1 siRNA group followed by analysis of Sirt1 level by Real-time PCR, cell proliferation by MTT assay, expression of OC, OPN and FABP4 level by real time PCR, and β-Catenin/TCF1/Runx2 protein expression by Western blot. In OP group, Sirt1 expression was significantly increased and BMSCs proliferation was decreased along with reduced OC and OPN mRNA expression, increased FABP4 expression and reduced β-Catenin/TCF1/Runx2 expression compared with sham operation group (P < 0.05). In Sirt1 siRNA group, Sirt1 expression was significantly reduced, BMSCs proliferation was increased, OC and OPN mRNA expression was increased, FABP4 expression was decreased, and β-Catenin/TCF1/Runx2 expression was increased compared to OP group (P < 0.05). Sirt1 is increased in osteoporosis. Down-regulating Sirt1 in osteoporotic BMSCs can regulate β-Catenin/TCF1/Runx2 signaling and promote BMSCs osteogenic differentiation and inhibit adipogenic differentiation.

Effects of macrophages and CXCR2 on adipogenic differentiation of bone marrow mesenchymal stem cells

2018 ◽  
Vol 234 (6) ◽  
pp. 9475-9485 ◽  
Author(s):  
Dingding Cao ◽  
Feifei Ma ◽  
Shengrong Ouyang ◽  
Zhuo Liu ◽  
Yuanyuan Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Bone marrow mesenchymal stem cells overexpressing hepatocyte growth factor ameliorate hypoxic–ischemic brain damage in neonatal rats

2021 ◽  
Vol 12 (1) ◽  
pp. 561-572
Author(s):  
Wen Zeng ◽  
Yu Wang ◽  
Yufeng Xi ◽  
Guoqing Wei ◽  
Rong Ju
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Neuroprotective Effects ◽  
Western Blots ◽  
Ischemic Brain ◽  
Marrow Mesenchymal Stem Cells ◽  
Hepatocyte Growth

Abstract Objectives Hypoxic–ischemic brain damage (HIBD) is a major cause of brain injury in neonates. Bone marrow mesenchymal stem cells (BMSCs) show therapeutic potential for HIBD, and genetic modification may enhance their neuroprotective effects. The goal of this study was to investigate the neuroprotective effects of hepatocyte growth factor (HGF)-overexpressing BMSCs (BMSCs-HGF) against HIBD and their underlying mechanisms. Methods: BMSCs were transfected with HGF using adenoviral vectors. HIBD models were established and then BMSCs were transplanted into the brains of HIBD rats via intraventricular injection. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to measure cerebral infarction volumes. In vitro, primary cultured cortical neurons were co-cultured with BMSCs in a Transwell plate system. Oxygen–glucose deprivation (OGD) was applied to imitate hypoxic–ischemic insult, and PD98059 was added to the culture medium to block the phosphorylation of extracellular signal-regulated kinase (ERK). Cell apoptosis was determined using TUNEL staining. The expression of HGF was measured by immunofluorescence, real-time quantitative PCR (RT-qPCR), and western blots. The expression of phosphorylated ERK (p-ERK) and B-cell lymphoma-2 (Bcl-2) was measured by western blots. Results HGF-gene transfection promoted BMSC proliferation. Moreover, BMSCs-HGF decreased HIBD-induced cerebral infarction volumes and enhanced the protective effects of the BMSCs against HIBD. BMSCs-HGF also increased expression of HGF, p-ERK, and Bcl-2 in brain tissues. In vitro, BMSC-HGF protected neurons against OGD-induced apoptosis. Inhibition of ERK phosphorylation abolished the neuroprotective effect of BMSCs-HGF against OGD. Conclusions BMSCs-HGF is a potential treatment for HIBD and that the ERK/Bcl-2 pathway is involved in the underlying neuroprotective mechanism.

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