Deferoxamine promotes osteoblastic differentiation in human periodontal ligament cells via the nuclear factor erythroid 2‐related factor‐mediated antioxidant signaling pathway

Chung, Joo Ho; Kim, Y S; Noh, Kwantae; Lee, Y M; Chang, Seok Woo; Kim, E C

doi:10.1111/jre.12136

Cited by 39 publications

(40 citation statements)

References 65 publications

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“…27,28 In contrast, human periodontal ligament cells do not seem to be particularly sensitive to DFO, as even concentrations of up to 200 mM still exerted pro-osteogenic effects. 26 In our hands, DFO reduced human BMSC viability at similar concentrations as murine BMSC (i.e., 50 mM, data not shown). However, it should be noted that the impact on cell viability did not seem to be of biological significance, as osteoblasts treated with 50 mM still differentiate better than untreated cells.…”

Section: Discussionmentioning

confidence: 52%

“…Our study is in line with a number of other studies that have shown an osteoblast-supporting effect of DFO. [26][27][28]44,45 Interestingly, osteoblasts treated with 50 mM DFO showed a somewhat decreased mineralization potential as compared to 25 mM DFO, indicating that this concentration might already exert toxic effects. In fact, we found a reduced cell viability in murine cells treated with 50 mM DFO, while cell vitality was not affected at 25 mM.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22] In contrast, osteoblast function is suppressed by iron excess in osteoblast cell lines, [23][24][25] while iron chelation using deferoxamine (DFO) seems to exert positive effects on osteoblast maturation. [26][27][28] In addition, bone regeneration during distraction osteogenesis and after radiation therapy has been shown to be promoted in the presence of DFO. [29][30] However, some studies have reported an inhibitory effect of DFO on osteoblasts and a suppression of alkaline phosphatase (ALP).…”

Section: Introductionmentioning

confidence: 99%

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Wnt5a is a key target for the pro-osteogenic effects of iron chelation on osteoblast progenitors

et al. 2016

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Wnt5a is a key target for the pro-osteogenic effects of iron chelation on osteoblast progenitors

et al. 2016

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“…Baschant et al showed that attenuated osteogenic differentiation was observed in the presence of excess iron, whereas elevated osteogenic differentiation was observed in the presence of the iron chelator (DFO) [25]. Chung et al discovered that long-term treatment with 200 µM DFO could promote the mineralization of human periodontal ligament cells [16]. In the present study, we observed that short-term treatment with a low concentration of iron chelator (10 µM DFO) at the early stages of mineralization could promote the differentiation and mineralization of DPSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Chung et al discovered that DFO treatment could promote the generation of Reactive Oxygen Species (ROS) through sequestering intracellular iron in normal cells [16]. It is well established that ROS is one prominent inducer for autophagy.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Jiang

et al. 2017

Cell Physiol Biochem

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Background/Aims: As a vital degradation and recycling system, autophagy plays an essential role in regulating the differentiation of stem cells. We previously showed that iron chelator deferoxamine (DFO) could promote the repair ability of dental pulp stem cells (DPSCs). Here, we investigated the effect of DFO in autophagy and the role of autophagy in regulating the migration and odontoblast differentiation of DPSCs. Methods: Transmission electron microscopy, immunofluorescence staining and western blotting were performed to evaluate the autophagic activity of DPSCs. Transmigration assay, alkaline phosphatase staining/activity, alizarin red S staining and quantitative PCR were performed to examine the migration and odontoblast differentiation of DPSCs. Reactive oxygen species (ROS) levels and the effects of ROS scavenger in autophagy induction were also detected. Autophagy inhibitors (3-MA and bafilomycin A1) and lentiviral vectors carrying ATG5 shRNA sequences were used for autophagy inhibition. Results: Early exposure to DFO promoted the mineralization of DPSCs and increased autophagic activity. Autophagy inhibition suppressed DFO-induced DPSC migration and odontoblast differentiation. Furthermore, DFO treatment could induce autophagy partly through hypoxia-inducible factor 1α/B cell lymphoma 2/adenovirus E1B 19K-interacting protein 3 (HIF-1α/BNIP3) pathway in a ROS-dependent manner. Conclusion: DFO increased DPSC migration and differentiation, which might be modulated through ROS-induced autophagy.

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Deferoxamine released from poly(lactic‐co‐glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis

Jia

Chen

Kang

et al. 2016

J Biomedical Materials Res

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The regeneration capacity of osteoporotic bones is generally lower than that of normal bones. Current methods of osteoporotic bone defect treatment are not always satisfactory. Recent studies demonstrate that activation of the hypoxia inducible factor-1α (HIF-1α) pathway, by genetic methods or hypoxia-mimicking agents, could accelerate bone regeneration. However, little is known as to whether modulating the HIF-1α pathway promotes osteoporotic defect healing. To address this problem in the present study, we first demonstrated that HIF-1α and vascular endothelial growth factor expression levels are lower in osteoporotic bones than in normal bones. Second, we loaded poly(Lactic-co-glycolic acid) (PLGA) with the hypoxia-mimetic agent deferoxamine (DFO). DFO released from PLGA had no significant effect on the proliferation of mesenchymal stem cells (MSCs); however, DFO did enhance the osteogenic differentiation of MSCs. In addition, DFO upregulated the mRNA expression levels of angiogenic factors in MSCs. Endothelial tubule formation assays demonstrate that DFO promoted angiogenesis in human umbilical vein endothelial cells. Third, untreated PLGA scaffolds (PLGA group) or DFO-containing PLGA (PLGA + DFO group) were implanted into critically sized osteoporotic femur defects in ovariectomized rats. After treatment periods of 14 or 28 days, micro-CT, histological, CD31 immunohistochemical, and dynamic bone histomorphometric analyses showed that DFO dramatically stimulated bone formation and angiogenesis in a critically sized osteoporotic femur defect model. Our in vitro and in vivo results demonstrate that DFO may promote the healing of osteoporotic bone defects due to enhanced angiogenesis and osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2515-2527, 2016.

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Deferoxamine promotes osteoblastic differentiation in human periodontal ligament cells via the nuclear factor erythroid 2‐related factor‐mediated antioxidant signaling pathway

Abstract: These data indicate, for the first time, that nontoxic DFO promotes osteoblastic differentiation of hPDLCs via modulation of the Nrf2-mediated antioxidant pathway.

Cited by 39 publications

References 65 publications

Wnt5a is a key target for the pro-osteogenic effects of iron chelation on osteoblast progenitors

Wnt5a is a key target for the pro-osteogenic effects of iron chelation on osteoblast progenitors

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

Deferoxamine released from poly(lactic‐co‐glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis

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