caa a22 4500 606235868 CHVBK 20210128101244.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s11010-015-2559-z doi (NATIONALLICENCE)springer-10.1007/s11010-015-2559-z Irradiation inhibits the maturation and mineralization of osteoblasts via the activation of Nrf2/HO-1 pathway [Elektronische Daten] [Sung-Ho Kook, Kyoung-A Kim, Hyeok Ji, Daewoo Lee, Jeong-Chae Lee] Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates the induction of antioxidant gene expression and protects cells against oxidative injury. However, there are controversial findings regarding the roles of Nrf2 on bone metabolism under oxidative stress. The role of Nrf2 on the differentiation of radiation-exposed osteoblasts is also unclear. We investigated whether Nrf2 negatively or positively affects osteoblast differentiation in response to irradiation. Irradiation inhibited osteoblast differentiation of MC3T3-E1 cells in a dose-dependent manner. This inhibition was evidenced by the irradiation-mediated decreases in bone-like nodule formation, alkaline phosphatase (ALP) activity, calcium accumulation, and expression of osteoblast markers, such as ALP, osteocalcin, osteopontin, bone sialoprotein, osterix, and Runx2. These reductions were accompanied by increased induction of Nrf2 and heme oxygenase-1 (HO-1), accumulation of cellular oxidants, and depletion of antioxidant defense enzymes. siRNA-mediated silencing of Nrf2 markedly reversed the negative effect of irradiation on osteoblast differentiation of the cells, leading to a decrease in HO-1 and an increase in Runx2 levels. Irradiation-mediated decreases in the levels of Runx2 and osteocalcin mRNA, but not of Nrf2 protein, were also significantly inhibited by HO-1 inhibitor, zinc protoporphyrin IX. Furthermore, N-acetyl cysteine restored all of the changes induced by irradiation to near-normal levels in the cells. These results demonstrate that irradiation inhibits osteoblast differentiation and mineralization of MC3T3-E1 cells through the oxidative stress-mediated activation of Nrf2/HO-1 pathway. Springer Science+Business Media New York, 2015 Irradiation nationallicence Osteoblast differentiation nationallicence Nrf2 nationallicence HO-1 nationallicence Runx2 nationallicence Kook Sung-Ho Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, 561-756, Jeonju, South Korea aut Kim Kyoung-A Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, 561-756, Jeonju, South Korea aut Ji Hyeok Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, 561-756, Jeonju, South Korea aut Lee Daewoo Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, 561-756, Jeonju, South Korea aut Lee Jeong-Chae Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, 561-756, Jeonju, South Korea aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 255-266 0300-8177 410:1-2<255 2015 410 11010 https://doi.org/10.1007/s11010-015-2559-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2559-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kook Sung-Ho Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, 561-756, Jeonju, South Korea aut NATIONALLICENCE 700 1- Kim Kyoung-A Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, 561-756, Jeonju, South Korea aut NATIONALLICENCE 700 1- Ji Hyeok Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, 561-756, Jeonju, South Korea aut NATIONALLICENCE 700 1- Lee Daewoo Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, 561-756, Jeonju, South Korea aut NATIONALLICENCE 700 1- Lee Jeong-Chae Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, 561-756, Jeonju, South Korea aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 255-266 0300-8177 410:1-2<255 2015 410 11010