Comparison the effects of hypoxia-mimicking agents on migration-related signaling pathways in mesenchymal stem cells

Heirani‐Tabasi, Asieh; Mirahmadi, Mahdi; Mishan, Mohammad Amir; Naderi‐Meshkin, Hojjat; Toosi, Shirin; Matin, Maryam Moghaddam; Bidkhori, Hamid Reza; Bahrami, Ahmad Reza

doi:10.1007/s10561-020-09851-2

Cited by 6 publications

(6 citation statements)

References 46 publications

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“…Xia Yi et.al have indicated that CAMK2A involves in the regulation of adipogenesis and osteoblastogenesis from human bone marrow mesenchymal stem cells [23]. Heirani-Tabasi A et.al have indicated that MAPK4 participates in the migration of adipose-derived mesenchymal stem cells under hypoxia-mimicking agents [24]. Li L et.al have indicated that RGS4 protects against osteoporosis through the LINC_00370-miR_222_3p-RGS4 axis.…”

Section: Discussionmentioning

confidence: 99%

The Integrative Analysis of Competitive Endogenous RNA Regulatory Networks in Osteoporosis

Sun

Wang

et al. 2022

Preprint

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Background: Osteoporosis (OP) is a common bone disease of old age resulting from the imbalance between bone resorption and bone formation. circRNAs are a class of endogenous noncoding RNAs (ncRNAs) involved in gene regulation and may play important roles in the development of OP. Here, we aimed to discover the OP‑related circRNA-miRNA-mRNA (ceRNA) network and the potential mechanisms.Results: Six datasets were obtained from GEO databases and the differentially expressed genes, circRNAs, and miRNAs were screened out from these datasets. Then, combined with the predicted target miRNAs and target genes, a total of 7 target circRNAs, 5 target miRNAs, 38 target genes, and a ceRNA network was constructed. Then RNA-seq verification by using total RNA isolated from the femurs of normal and oophorectomy Wistar rats indicated that MFAP5, CAMK2A, and RGS4 were closely associated with osteoporosis. Function enrichment analysis indicated that the target circRNAs, miRNAs, and genes were involved in the process of MAPK cascade, hormone stimulus, cadherin binding, rRNA methyltransferase, PI3K-Akt signaling pathway, and Vitamin digestion and absorption, et.al. Then a circRNA-miRNA-hub gene subnetwork was constructed and the RT-qPCR analysis of human bone tissues from the femoral head was used to confirm that the transcription of hsa_circR_0028877, hsa_circR_0082916, DIRAS2, CAMK2A, and MAPK4 showed a significant correlation with osteogenic genes. Besides, the two axes of hsa_circR_0028877 - hsa-miR-1273f - CAMK2A and hsa_circR_0028877 - hsa-miR-1273f - DIRAS2 conformed to be closely associated with OP. Additionally, by constructing a drug-target gene network, RKI-1447, FRAX486, Hyaluronic, and Fostamatinib were identified as therapeutic options for OP.Conclusions: Our study revealed the potential links between circRNAs, miRNAs, and mRNAs in OP, suggesting that the ceRNA mechanism may contribute to the occurrence of OP.

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Section: Discussionmentioning

confidence: 99%

The Integrative Analysis of Competitive Endogenous RNA Regulatory Networks in Osteoporosis

Sun

Wang

et al. 2022

Preprint

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“…DFO could increase both cell migration and expression of genes such as VEGF‐A, VEGF‐C, MAPK4, INPP4B and IL‐8. 91 Various studies have exploited this mechanism for inducing HIF‐mediated responses. 92 , 93 Alternatively, inhibition of PHD through oxoglutarate analogues such as dimethyloxalyglycine (DMOG) can inhibit the hydroxylation of HIF‐1α similar to culturing cells under hypoxic conditions (12.5%‐2.5%).…”

Section: Hypoxia‐inducing Chemicalsmentioning

confidence: 99%

Engineering Tools for Regulating Hypoxia in Tumour Models

Kim

Green

Lin

et al. 2021

J Cellular Molecular Medi

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Major advances in the field of genomic technologies have led to an improvement in cancer diagnosis, classification and prognostication. However, many cancers remain incurable due to the development of drug resistance, minimal residual disease (MRD) and disease relapse, highlighting an incomplete understanding of the mechanisms underlying these processes. In recent years, the impact of non‐genetic factors on neoplastic transformations has increasingly been acknowledged, and growing evidence suggests that low oxygen (O2) levels (ie hypoxia) in the tumour microenvironment play a critical role in the development and treatment of cancer. As a result, there is a growing need to develop research tools capable of reproducing physiologically relevant O2 conditions encountered by cancer cells in their natural environments in order to gain in‐depth insight into tumour cell metabolism and function. In this review, the authors highlight the importance of hypoxia in the pathogenesis of malignant diseases and provide an overview of novel engineering tools that have the potential to further drive this evolving, yet technically challenging, field of cancer research.

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“…Cell migration is a fundamental biological process involved in tissue homeostasis and is an important part of cell transplantation. It has a complex mechanism which is still not clear and may be related to the MAPK signaling pathway, phosphatidylinositol signaling pathway and cytokine-cytokine receptor pathway [40,41]. Many studies have shown that cells migrate faster under hypoxia than normoxia, including mesenchymal stem cells and carcinoma cells [42][43][44].…”

Section: Cell Migrationmentioning

confidence: 99%

“…They concluded that HIF1α independent mechanisms modulate the divergent outcomes in assembly of fibronectin, which is a core matrix protein that assembles to promote cell migration. Heirani-Tabasi et al [41] compared the effects of three hypoxia-mimicking agents on migration-related signaling pathways in mesenchymal stem cells and found that CoCl 2 failed to promote cell migration and the mechanism of which may be partly related to the MAPK signaling pathway through IL8/CXCR2 axis or similar mechanisms. In addition, some studies found that CoCl 2 inhibited cell migration compared with normoxia [2,45].…”

Section: Cell Migrationmentioning

confidence: 99%

The biological effect of cobalt chloride mimetic-hypoxia on nucleus pulposus cells and the comparability with physical hypoxia in vitro

Gao

et al. 2021

Front. Biosci. (Landmark Ed)

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Objective: Nucleus pulposus cells (NPCs) are cells extracted from the intervertebral disc and are important for research into intervertebral disc degeneration (IVDD). NPCs live in an avascular and relatively hypoxic environment. Cobalt chloride (CoCl2) has been used in many cell studies to mimic hypoxia. The objective of this study was to explore the possibility of using CoCl2 to induce mimetic-hypoxia for NPCs and the comparison with hypoxia (1% O2) in vitro. Materials and methods: Rat nucleus pulposus cells of Passage 3–5 were used in this research. Cell viability, rate of cell apoptosis, ROS (reactive oxygen species) generation, cell migration, extracellular pH and extracellular matrix metabolism were determined to compare the influence of hypoxia (1% O2) and CoCl2 on NPCs. Results: We found that the effects of CoCl2 on NPCs was dose-dependent. At the proper concentration, CoCl2 could be used to elicit chemical hypoxia for nucleus pulposus cells in vitro and many biological effects, analogous to physical hypoxia (1% O2), could be achieved such as enhanced cell viability, decreased apoptosis and activated extracellular matrix metabolism. On the other hand, CoCl2 mimetic-hypoxia did not affect NPCs glycolysis and migration compared to physical hypoxia. In addition, high concentration of CoCl2 (>200 μM) is harmful to NPCs with high rates of apoptosis and ECM (extracellular matrix) degradation. Conclusions: It is feasible and convenient to use CoCl2 to induce chemical mimetic hypoxia for culturing NPCs on the premise of appropriate concentration. But in aspects of cell migration and glycolysis, CoCl2 could not achieve similar results with physical hypoxia. This study may provide a convenient method and enlightenment to induce mimetic-hypoxia for researchers studying NPCs and IVVD.

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Comparison the effects of hypoxia-mimicking agents on migration-related signaling pathways in mesenchymal stem cells

Cited by 6 publications

References 46 publications

The Integrative Analysis of Competitive Endogenous RNA Regulatory Networks in Osteoporosis

The Integrative Analysis of Competitive Endogenous RNA Regulatory Networks in Osteoporosis

Engineering Tools for Regulating Hypoxia in Tumour Models

The biological effect of cobalt chloride mimetic-hypoxia on nucleus pulposus cells and the comparability with physical hypoxia in vitro

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