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Glucose oxidase facilitates osteogenic differentiation and mineralization of embryonic stem cells through the activation of Nrf2 and ERK signal transduction pathways

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Abstract

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) signal is known to play important roles in controlling bone homeostasis. This study examined how oxidative stress affects the mineralization of embryonic stem (ES) cells by exposing them to glucose oxidase (GO), which continuously generates H2O2 at low concentrations. The roles of Nrf2/HO-1 and mitogen-activated protein kinases on osteogenesis in GO-exposed ES cells were also investigated. GO treatment at relatively low concentrations did not change the viability of ES cells, whereas it enhanced osteogenic differentiation and mineralization in the cells. GO treatment (1 mU/ml) augmented the induction of runt-related transcription factor 2 (Runx2), Nrf2, and HO-1 in ES cells. GO-mediated acceleration of Runx2 expression and mineralization was inhibited either by Nrf2 knockdown or by treating with 5 μM PD98059, an inhibitor of phospho-extracellular signal-regulated kinase (p-ERK). The GO-stimulated mineralization was also suppressed by treating the cells with reduced glutathione or catalase, but not by superoxide dismutase or N-acetyl-cysteine. Collectively, our results demonstrate that a mild oxidative stress activates Nrf2/HO-1 signaling and an ERK-mediated pathway, and facilitates the mineralization of ES cells with a corresponding increase in Runx2.

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Acknowledgments

This paper was supported by Fund of Biomedical Research Institute, Chonbuk National University Hospital.

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    Authors and Affiliations

    1. Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Chonbuk National University, Jeonju, 54896, South Korea

      Hyun-Jaung Sim, Sung-Ho Kook & Jeong-Chae Lee

    2. Cluster for Craniofacial Development & Regeneration Research, Institute of Oral Biosciences, Chonbuk National University, Jeonju, 54896, South Korea

      Hyun-Jaung Sim, Sung-Ho Kook, Seung-Youp Lee & Jeong-Chae Lee

    3. Chonnam National University Dental Hospital, Kwangju, 61186, South Korea

      Jae-Hwan Kim

    4. Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, 54896, South Korea

      Seung-Youp Lee & Jeong-Chae Lee

    5. Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju, 54896, South Korea

      Jeong-Chae Lee

    6. Research Institute of Clinical Medicine of Chonbuk National University, Jeonju, 54896, South Korea

      Seung-Youp Lee

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    1. Hyun-Jaung Sim
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    Correspondence to Seung-Youp Lee or Jeong-Chae Lee.

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    Hyun-Jaung Sim and Jae-Hwan Kim have contributed equally to this work.

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    Sim, HJ., Kim, JH., Kook, SH. et al. Glucose oxidase facilitates osteogenic differentiation and mineralization of embryonic stem cells through the activation of Nrf2 and ERK signal transduction pathways. Mol Cell Biochem 419, 157–163 (2016). https://doi.org/10.1007/s11010-016-2760-8

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    • DOI: https://doi.org/10.1007/s11010-016-2760-8

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