scholarly journals Lenalidomide restores the osteogenic differentiation of bone marrow mesenchymal stem cells from multiple myeloma patients via deactivating Notch signaling pathway

Oncotarget ◽  
2017 ◽  
Vol 8 (33) ◽  
pp. 55405-55421 ◽  
Author(s):  
Juan Guo ◽  
Chengming Fei ◽  
Youshan Zhao ◽  
Sida Zhao ◽  
Qingqing Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Notch Signaling ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Effect of NTN and Lmx1α on the Notch Signaling Pathway during the Differentiation of Human Bone Marrow Mesenchymal Stem Cells into Dopaminergic Neuron-Like Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jinhua Zhang ◽  
Bo Yang ◽  
Lilin Luo ◽  
Linhui Li ◽  
Xuantao Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Dopaminergic Neuron ◽  
Notch Signaling Pathway ◽  
Control Group ◽  
Marrow Mesenchymal Stem Cells

Human bone marrow mesenchymal stem cells (h-BMSCs) have the potential to differentiate into dopaminergic neuron-like cells to treat Parkinson’s disease. The Notch signaling pathway has been implicated in the regulation of cell fate decisions such as differentiation of BMSCs. This study investigated changes in the expression of Notch-related genes in the differentiation of BMSCs in vitro into dopaminergic (DA) neuron-like cells. BMSCs transfected with empty lentiviral vectors served as the control group and those transfected with NTN and Lmx1α recombinant lentiviral vectors served as the experimental group. After induction and culture of NTN and Lmx1α-transfected h-BMSCs for 21 days, the cells exhibited features of dopaminergic neuron-like cells, which were observed by transmission and scanning electron microscopy and verified by immunofluorescence of tyrosine hydroxylase (TH) and dopamine transporter (DAT). These induced cells could secrete dopamine and had basic action potentials. Expression of the neural stem cell (NSC) markers, including octamer-binding protein (Oct4), paired box gene 6 (Pax6), and sex determining region Y-box 1 (SOX1), increased on day 14 of induction and decreased on day 21 of induction during differentiation. The human Notch signaling pathway PCR array showed a differential expression of Notch-related genes during the differentiation of h-BMSCs into DA neuron-like cells in vitro relative to that in the control group. In conclusion, h-BMSCs overexpressing NTN and Lmx1α can successfully be induced to differentiate into dopaminergic neuron-like cells with a neuronal phenotype exhibiting fundamental biological functions in vitro, and NTN and Lmx1α may affect the expression of Notch-related genes during differentiation.

scholarly journals Icariin Promotes the Osteogenesis of Bone Marrow Mesenchymal Stem Cells through Regulating Sclerostin and Activating the Wnt/β-Catenin Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jianliang Gao ◽  
Shouyu Xiang ◽  
Xiao Wei ◽  
Ram Ishwar Yadav ◽  
Menghu Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Fragility Fractures ◽  
Therapeutic Efficiency ◽  
Increased Risk ◽  
Marrow Mesenchymal Stem Cells ◽  
Osteogenic Induction

Osteoporosis (OP) is a metabolic disease characterized by decreased bone mass and increased risk of fragility fractures, which significantly reduces the quality of life. Stem cell-based therapies, especially using bone marrow mesenchymal stem cells (BMSCs), are a promising strategy for treating OP. Nevertheless, the survival and differentiation rates of the transplanted BMSCs are low, which limits their therapeutic efficiency. Icariin (ICA) is a traditional Chinese medicine formulation that is prescribed for tonifying the kidneys. It also promotes the proliferation and osteogenic differentiation of BMSCs, although the specific mechanism remains unclear. Based on our previous research, we hypothesized that ICA promotes bone formation via the sclerostin/Wnt/β-catenin signaling pathway. We isolated rat BMSCs and transfected them with sclerostin gene (SOST) overexpressing or knockdown constructs and assessed osteogenic induction in the presence or absence of ICA. Sclerostin significantly inhibited BMSC proliferation and osteogenic differentiation, whereas the presence of ICA not only increased the number of viable BMSCs but also enhanced ALP activity and formation of calcium nodules during osteogenic induction. In addition, the osteogenic genes including Runx2, β-catenin, and c-myc as well as antioxidant factors (Prdx1, Cata, and Nqo1) were downregulated by sclerostin and restored by ICA treatment. Mechanistically, ICA exerted these effects by activating the Wnt/β-catenin pathway. In conclusion, ICA can promote the proliferation and osteogenic differentiation of BMSCs in situ and therefore may enhance the therapeutic efficiency of BMSC transplantation in OP.

scholarly journals Morusin induces osteogenic differentiation of bone marrow mesenchymal stem cells by canonical Wnt/β-catenin pathway and prevents bone loss in an ovariectomized rat model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Chen ◽  
Hui Han ◽  
Siqi Zhou ◽  
Yinxian Wen ◽  
Liaobin Chen
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Nuclear Translocation ◽  
Osteoclast Differentiation ◽  
Alizarin Red ◽  
Marrow Mesenchymal Stem Cells

Abstract Background Osteoporosis (OP) is a metabolic bone disease due to the imbalance of osteogenesis and bone resorption, in which, bone marrow mesenchymal stem cells (BMSCs) have a significant effect as the seed cells. Recent research has shown the function of Morusin on inhibiting osteoclast differentiation in vitro. However, whether Morusin can regulate the osteogenic differentiation in addition to the proliferation of BMSCs remains unclear. Methods BMSCs were isolated from 4-week-old Wistar rats and then treated with different concentrations of Morusin for 3, 5, 7, and 14 days. The proliferation of BMSCs was detected by MTT assay. The effect of Morusin on osteogenic differentiation of BMSCs was detected by RT-qPCR, Western blotting, ALP, and Alizarin Red staining. The effect of Morusin on Wnt/β-catenin signaling pathway was analyzed by RT-qPCR, Western blotting, and immunofluorescence. Finally, in the ovariectomy-induced osteoporosis model, the anti-osteoporosis activity of Morusin was determined by micro-CT, HE, and immunohistochemistry. Results The results showed the function of 2.5–10 μM Morusin in the promotion of the proliferation in addition to osteogenic differentiation of BMSCs. Moreover, it also has an impact in activating the Wnt/β-catenin signaling pathway via inhibition of β-catenin phosphorylation as well as promotion of its nuclear translocation. Upon Dickkopf-related protein-1 (DKK-1, an inhibitor of the Wnt/β-catenin signaling pathway) was added to the Morusin, Morusin had a decreased stimulatory osteogenic effect on BMSCs. Finally, in the rat OP model, we found that Morusin could also exert anti-osteoporosis activity in vivo. Conclusions This study indicates the ability of Morusin in the promotion of osteogenic differentiation of BMSCs via the activation of Wnt/β-catenin signaling pathway and also shows the potential of Morusin to be an agent for osteoporosis treatment.

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