scholarly journals A Core Omnigenic Non-coding Trait Governing Dex-Induced Osteoporotic Effects Identified Without DEXA

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Lu ◽  
Yanzhen Cai ◽  
Xiaoling Luo ◽  
Zhangting Wang ◽  
Sin Hang Fung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Loss ◽  
Regulatory Network ◽  
Genetic Background ◽  
Scavenger Receptor ◽  
Transcriptome Profiling ◽  
Akt Pathway ◽  
Epigenetic Changes ◽  
Phenotypic Changes

Iatrogenic glucocorticoid (GC)-induced osteoporosis (GIO) is an idiosyncratic form of secondary osteoporosis. Genetic predisposition among individuals may give rise to variant degree of phenotypic changes but there has yet been a documented unified pathway to explain the idiosyncrasy. In this study, we argue that the susceptibility to epigenetic changes governing molecular cross talks along the BMP and PI3K/Akt pathway may underline how genetic background dictate GC-induced bone loss. Concordantly, osteoblasts from BALB/c or C57BL/6 neonatal mice were treated with dexamethasone for transcriptome profiling. Furthermore, we also confirmed that GC-pre-conditioned mesenchymal stem cells (MSCs) would give rise to defective osteogenesis by instigating epigenetic changes which affected the accessibility of enhancer marks. In line with these epigenetic changes, we propose that GC modulates a key regulatory network involving the scavenger receptor Cd36 in osteoblasts pre-conditioning pharmacological idiosyncrasy in GIO.

Valsartan impairs angiogenesis of mesenchymal stem cells through Akt pathway

2013 ◽  
Vol 167 (6) ◽  
pp. 2765-2774 ◽  
Author(s):  
Cheng-I Cheng ◽  
Chang-Chun Hsiao ◽  
Shinn-Chih Wu ◽  
Shao-Yu Peng ◽  
Hon-Kan Yip ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Akt Pathway

scholarly journals High Throughput Transcriptome Profiling of Lithium Stimulated Human Mesenchymal Stem Cells Reveals Priming towards Osteoblastic Lineage

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e55769 ◽  
Author(s):  
Neeraj Kumar Satija ◽  
Deepa Sharma ◽  
Farhat Afrin ◽  
Rajendra P. Tripathi ◽  
Gurudutta Gangenahalli
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
High Throughput ◽  
Human Mesenchymal Stem Cells ◽  
Transcriptome Profiling ◽  
Osteoblastic Lineage

scholarly journals Human Mesenchymal Stem Cells Derived Exosomes Inhibit the Growth of Acute Myeloid Leukemia Cells via Regulating miR-23b-5p/TRIM14 Pathway

2021 ◽  
Author(s):  
hui cheng ◽  
Jie Ding ◽  
Gusheng Tang ◽  
Aijie Huang ◽  
Lei Gao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Mesenchymal Stem Cells ◽  
Myeloid Leukemia ◽  
Human Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cell ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is a malignancy commonly seen in adults. Previous studies indicated that TRIM14 played a tumorigenic role in various types of cancer and miR-23b-5p was down-regulated in human mesenchymal stem cell-derived exosomes (HMSC-exos) of AML patients. However, their roles in AML remains unclear. Our study aims to investigate the role of TRIM14 and miR-23b-5p in the pathogenesis of AML.Materials and methods: The blood specimen was collected from AML patients and healthy donators. Exosomes were extracted from the culture medium of human mesenchymal stem cells under ultracentrifugation. Then exosomes were co-cultured with AML cells to determine the effect of their contents. The cell proliferation was detected by cell counting kit-8 assay, whereas the cell apoptosis was detected by flow cytometry. The expression of miR-23b-5p and TRIM14 was silenced or overexpressed to explore their biological functions in AML. Luciferase reporter assay was conducted to validate the interaction between miR-23b-5p and TRIM14. Gene expression was determined by quantitative real-time PCR and immunoblots.Results: TRIM14 was significantly increased in AML patients and cell lines. The inhibition of TRIM14 significantly reduced the proliferation and induced the apoptosis of AML cells via activating PI3K/AKT pathway, whereas its overexpression exhibited reversed effects. HMSC-exos could suppress the proliferation of AML cells through the delivery of miR-23b-5p. Moreover, miR-23b-5p inhibited the transcription of TRIM14 by binding on its 3’UTR region. Overexpression of TRIM14 exhibited reversed effect against the function of miR-23b-5p mimic.Conclusion: TRIM14 could promote the proliferation of AML cells via activating PI3K/AKT pathway, which was reversed by HMSC-exos through delivering miR-23b-5p. These findings indicated that miR-23b-5p and TRIM14 could be applied as potential targets for the treatment of AML.

scholarly journals Mesenchymal Stem Cells and NF-κB Sensing Interleukin-4 Over-Expressing Mesenchymal Stem Cells Are Equally Effective in Mitigating Particle-Associated Chronic Inflammatory Bone Loss in Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Ning Zhang ◽  
Takeshi Utsunomiya ◽  
Tzuhua Lin ◽  
Yusuke Kohno ◽  
Masaya Ueno ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Loss ◽  
Chronic Inflammation ◽  
Local Injection ◽  
Interleukin 4 ◽  
M2 Macrophage ◽  
Mineral Density ◽  
Primary Surgery ◽  
Polyethylene Particle

Wear particles from total joint arthroplasties (TJAs) induce chronic inflammation, macrophage infiltration and lead to bone loss by promoting bone destruction and inhibiting bone formation. Inhibition of particle-associated chronic inflammation and the associated bone loss is critical to the success and survivorship of TJAs. The purpose of this study is to test the hypothesis that polyethylene particle induced chronic inflammatory bone loss could be suppressed by local injection of NF-κB sensing Interleukin-4 (IL-4) over-expressing MSCs using the murine continuous polyethylene particle infusion model. The animal model was generated with continuous infusion of polyethylene particles into the intramedullary space of the femur for 6 weeks. Cells were locally injected into the intramedullary space 3 weeks after the primary surgery. Femurs were collected 6 weeks after the primary surgery. Micro-computational tomography (μCT), histochemical and immunohistochemical analyses were performed. Particle-infusion resulted in a prolonged pro-inflammatory M1 macrophage dominated phenotype and a decrease of the anti-inflammatory M2 macrophage phenotype, an increase in TRAP positive osteoclasts, and lower alkaline phosphatase staining area and bone mineral density, indicating chronic particle-associated inflammatory bone loss. Local injection of MSCs or NF-κB sensing IL-4 over-expressing MSCs reversed the particle-associated chronic inflammatory bone loss and facilitated bone healing. These results demonstrated that local inflammatory bone loss can be effectively modulated via MSC-based treatments, which could be an efficacious therapeutic strategy for periprosthetic osteolysis.

scholarly journals Upregulation of PTEN in Glioma Cells by Cord Blood Mesenchymal Stem Cells Inhibits Migration via Downregulation of the PI3K/Akt Pathway

PLoS ONE ◽  
2010 ◽  
Vol 5 (4) ◽  
pp. e10350 ◽  
Author(s):  
Venkata Ramesh Dasari ◽  
Kiranpreet Kaur ◽  
Kiran Kumar Velpula ◽  
Meena Gujrati ◽  
Daniel Fassett ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cord Blood ◽  
Glioma Cells ◽  
Akt Pathway

scholarly journals Transcriptome Profiling of IL-17A Preactivated Mesenchymal Stem Cells: A Comparative Study to Unmodified and IFN-γModified Mesenchymal Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Kisha Nandini Sivanathan ◽  
Darling Rojas-Canales ◽  
Shane T. Grey ◽  
Stan Gronthos ◽  
Patrick T. Coates
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Antigen Processing ◽  
Cellular Therapy ◽  
Human Mesenchymal Stem Cells ◽  
Humoral Response ◽  
Transcriptome Profiling ◽  
Antigen Processing And Presentation ◽  
Immunomodulatory Function

Human mesenchymal stem cells pretreatment with IL-17A (MSC-17) potently enhances T cell immunosuppression but not their immunogenicity, in addition to avidly promoting the induction of suppressive regulatory T cells. The aim of this study was to identify potential mechanisms by which human MSC-17 mediate their superior immunomodulatory function. Untreated-MSC (UT-MSC), IFN-γtreated MSC (MSC-γ), and MSC-17 were assessed for their gene expression profile by microarray. Significantly regulated genes were identified for their biological functions (Database for Annotation, Visualisation and Integrated Discovery, DAVID). Microarray analyses identified 1278 differentially regulated genes between MSC-γand UT-MSC and 67 genes between MSC-17 and UT-MSC. MSC-γwere enriched for genes involved in immune response, antigen processing and presentation, humoral response, and complement activation, consistent with increased MSC-γimmunogenicity. MSC-17 genes were associated with chemotaxis response, which may be involved in T cell recruitment for MSC-17 immunosuppression. MMP1, MMP13, and CXCL6 were highly and specifically expressed in MSC-17, which was further validated by real-time PCR. Thus, MMPs and chemokines may play a key role in mediating MSC-17 superior immunomodulatory function. MSC-17 represent a potential cellular therapy to suppress immunological T cell responses mediated by expression of an array of immunoregulatory molecules.

Advanced platelet-rich fibrin extract treatment promotes the proliferation and differentiation of Human Adipose-Derived Mesenchymal Stem Cells through activation of tryptophan metabolism

2021 ◽  
Vol 16 ◽  
Author(s):  
Guan-Ming Lu ◽  
Li-Yuan Jiang ◽  
Dong-Lin Huang ◽  
Yong-Xian Rong ◽  
Yang-Hong Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory Network ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Tryptophan Metabolism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Platelet Rich Fibrin ◽  
The Core ◽  
Proliferation And Differentiation

Background: Advanced platelet-rich fibrin extract (APRFE) contains a high concentration of various cytokines that are helpful for improving stem cells repair function. Objective: However, the underlying mechanism of APRFE improving stem cell repairing is not clear. Methods: We produced APRFE by centrifuging fresh peripheral blood samples and isolated and identified human adipose-derived mesenchymal stem cells (ADMSCs). The abundance of cytokines contained in APRFE was detected by the Enzyme-linked immunosorbent assay (ELISA). The ADMSCs treated with or without APRFE were collected for transcriptome sequencing. Results: Based on the sequencing data, the expression profiles were contracted. The differentially expressed genes and lncRNA (DEGs and DElncRNAs) were obtained using for the differential expression analysis. The lncRNA-miRNA-mRNA network was constructed based on the miRNet database. The further enrichment analysis results showed that the biological functions were mainly related to proliferation, differentiation, and cell-cell function. To explore the role of APRFE, the protein-protein interaction network was constructed among the cytokines included in APRFE and DEGs. Furthermore, we constructed the global regulatory network based on the RNAInter and TRRUST database. The pathways in the global regulatory network were considered as the core pathways. We found that the DEGs in the core pathways were associated with stemness scores. Conclusion: In summary, we predicted that APRFE activated three pathways (tryptophan metabolism, mTOR signaling pathway, and adipocytokine signaling) to promote the proliferation and differentiation of ADMSCs. The finding may be helpful for guiding the application of ADMSCs in the clinic.

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