Deferoxamine-Induced Migration and Odontoblast Differentiation via ROS-Dependent Autophagy in Dental Pulp Stem Cells

Wang, Xuan; Wu, Tian Tian; Jiang, Long; Du, Rong; Zhu, Ye

doi:10.1159/000484506

Cited by 24 publications

(23 citation statements)

References 38 publications

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“…The stromal-derived factor-1 alpha (SDF-1α)/CXCR4 axis plays a critical role in regulating the trafficking of MSCs toward the target tissue (Cencioni et al 2012). Previous studies have suggested that hypoxia and hypoxia-mimetic agents, such as CoCl 2 or deferoxamine (DFX), may increase the migration of MSCs by increasing the expression of CXCR4 (Li et al 2017;Wang et al 2017). Our study also found that CoCl 2 treatment enhanced SHED migration.…”

Section: Discussionsupporting

confidence: 62%

Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth

Chen

Zhao

Yang

et al. 2019

Cell Stress and Chaperones

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Stem cells from human exfoliated deciduous teeth (SHEDs) are a promising source for tissue engineering and stem cell transplantation. However, long-term in vitro culture and expansion lead to the loss of stemness of SHEDs, compromising their therapeutic benefits. Hypoxia plays an essential role in controlling the stem cell behavior of mesenchymal stem cells (MSCs). Thus, this study aimed to investigate the effects of cobalt chloride (CoCl 2), a hypoxia-mimetic agent, on the stem cell marker expression and osteogenic differentiation of SHEDs. SHEDs were cultured with or without 50 or 100 μM CoCl 2. Their proliferation, apoptosis, stem cell marker expression, migration ability, and osteogenic differentiation were examined. Culture with 50 and 100 μM CoCl 2 increased the hypoxiainducible factor-1 alpha (HIF-1α) protein levels in a dose-dependent manner in SHEDs without inducing significant cytotoxicity. This effect was accompanied by an increase in the proportion of STRO-1 + cells. CoCl 2 significantly increased the expression of stem cell markers (OCT4, NANOG, SOX2, and c-Myc) in a dose-dependent manner. The migration ability was also promoted by CoCl 2 treatment. Furthermore, SHEDs cultured in osteogenic medium with CoCl 2 showed a dose-dependent reduction in alkaline phosphatase (ALP) activity and calcium deposition. The expression of osteogenic-related genes was also suppressed by CoCl 2 , especially in the 100-μM CoCl 2 group. In conclusion, CoCl 2 increased the expression of stem cell markers and inhibited the osteogenic differentiation of SHEDs. These findings may provide evidence supporting the use of in vitro hypoxic environments mimicked by CoCl 2 in assisting the clinical application of SHEDs.

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Section: Discussionsupporting

confidence: 62%

Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth

Chen

Zhao

Yang

et al. 2019

Cell Stress and Chaperones

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“…The increased chelatable iron catalyzes excess Fenton reactions, contributing to the production of ROS [34,35,36,37,38]. Moreover, as a hypoxia-mimic compound, DFO increased ROS accumulation in various cells [20,21,39]. In the present study, DFO induced cellular and mitochondrial ROS generation in MCF-7 and MDA-MB-231 cells.…”

Section: Discussionmentioning

confidence: 52%

Deferoxamine Enhanced Mitochondrial Iron Accumulation and Promoted Cell Migration in Triple-Negative MDA-MB-231 Breast Cancer Cells Via a ROS-Dependent Mechanism

Chen

Wang

Liu

2019

IJMS

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In our previous study, Deferoxamine (DFO) increased the iron concentration by upregulating the expression levels of TfR1 and DMT1 and exacerbated the migration of triple-negative breast cancer cells. However, the mechanisms of iron distribution and utilization in triple-negative breast cancer cells with a DFO-induced iron deficiency are still unclear. In this study, triple-negative MDA-MB-231 and estrogen receptor (ER)-positive MCF-7 breast cancer cells were used to investigate the mechanisms of iron distribution and utilization with a DFO-induced iron deficiency. We found that the mitochondrial iron concentration was elevated in MDA-MB-231 cells, while it was decreased in MCF-7 cells after DFO treatment. The cellular and mitochondrial reactive oxygen species (ROS) levels increased in both breast cancer cell types under DFO-induced iron-deficient conditions. However, the increased ROS levels had different effects on the different breast cancer cell types: Cell viability was inhibited and apoptosis was enhanced in MCF-7 cells, but cell viability was maintained and cell migration was promoted in MDA-MB-231 cells through the ROS/NF-κB and ROS/TGF-β signaling pathways. Collectively, this study suggests that under DFO-induced iron-deficient conditions, the increased mitochondrial iron levels in triple-negative MDA-MB-231 breast cancer cells would generate large amounts of ROS to activate the NF-κB and TGF-β signaling pathways to promote cell migration.

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“…For instance, chetomin, an inhibitor of the HIF1A/p300 interaction, can inhibit tumor cell growth of MM (69). Due to the function of HIF1A in inducing autophagy, the suppressive effects of inhibitors of HIF1A could exert their effect by modulating the autophagy of MM cells (70)(71)(72)(73). The expression levels of EIF4EBP1, which is a target of mTOR, have been reported to be upregulated for MM cases (74).…”

Section: Discussionmentioning

confidence: 99%

A predicted risk score based on the expression of 16 autophagy‑related genes for multiple myeloma survival

Zhu¹,

Wang

Zeng³

et al. 2019

Oncol Lett

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Autophagy has an important role in the pathogenesis of plasma cell development and multiple myeloma (MM); however, the prognostic role of autophagy-related genes (ARGs) in MM remains undefined. In the present study, the expression profiles of 234 ARGs were obtained from a Gene Expression Omnibus dataset (accession GSE24080), which contains 559 samples of patients with MM analyzed with 54,675 probes. Univariate Cox regression analysis identified 55 ARGs that were significantly associated with event-free survival of MM. Furthermore, a risk score with 16 survival-associated ARGs was developed using multivariate Cox regression analysis, including ATIC,

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Deferoxamine-Induced Migration and Odontoblast Differentiation via ROS-Dependent Autophagy in Dental Pulp Stem Cells

Cited by 24 publications

References 38 publications

Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth

Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth

Deferoxamine Enhanced Mitochondrial Iron Accumulation and Promoted Cell Migration in Triple-Negative MDA-MB-231 Breast Cancer Cells Via a ROS-Dependent Mechanism

A predicted risk score based on the expression of 16 autophagy‑related genes for multiple myeloma survival

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