title: Glucose oxidase facilitates osteogenic differentiation and mineralization of embryonic stem cells through the activation of Nrf2 and ERK signal transduction pathways.
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.
authors.affiliation: Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Chonbuk National University, Jeonju, 54896, South Korea.|Cluster for Craniofacial Development & Regeneration Research, Institute of Oral Biosciences, Chonbuk National University, Jeonju, 54896, South Korea.
authors.forename: Hyun-Jaung
authors.initials: HJ
authors.lastname: Sim
authors.affiliation: Chonnam National University Dental Hospital, Kwangju, 61186, South Korea.
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Chonbuk National University, Jeonju, 54896, South Korea.|Cluster for Craniofacial Development & Regeneration Research, Institute of Oral Biosciences, Chonbuk National University, Jeonju, 54896, South Korea.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Kook
authors.affiliation: Cluster for Craniofacial Development & Regeneration Research, Institute of Oral Biosciences, Chonbuk National University, Jeonju, 54896, South Korea. j2j2j2j@jbnu.ac.kr.|Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, 54896, South Korea. j2j2j2j@jbnu.ac.kr.|Research Institute of Clinical Medicine of Chonbuk National University, Jeonju, 54896, South Korea. j2j2j2j@jbnu.ac.kr.
authors.forename: Seung-Youp
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Chonbuk National University, Jeonju, 54896, South Korea. leejc88@jbnu.ac.kr.|Cluster for Craniofacial Development & Regeneration Research, Institute of Oral Biosciences, Chonbuk National University, Jeonju, 54896, South Korea. leejc88@jbnu.ac.kr.|Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, 54896, South Korea. leejc88@jbnu.ac.kr.|Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju, 54896, South Korea. leejc88@jbnu.ac.kr.
authors.forename: Jeong-Chae
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D005949:Glucose Oxidase / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C493716:Runx2 protein, mouse; D005949:Glucose Oxidase
keywords: Embryonic stem cells; MAPK; Nrf2; Osteogenesis; Oxidative stress; Runx2