N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway

被引:56
作者
Lee, Daewoo [1 ,2 ]
Kook, Sung-Ho [1 ,2 ,3 ,4 ]
Ji, Hyeok [1 ,2 ]
Lee, Seung-Ah [5 ]
Choi, Ki-Choon [6 ]
Lee, Kyung-Yeol [1 ,2 ]
Lee, Jeong-Chae [1 ,2 ,3 ,4 ]
机构
[1] Chonbuk Natl Univ, Inst Oral Biosci, Jeonju 54896, South Korea
[2] Chonbuk Natl Univ, Sch Dent, Jeonju 54896, South Korea
[3] Chonbuk Natl Univ, Dept Bioact Mat Sci, Jeonju 54896, South Korea
[4] Chonbuk Natl Univ, Inst Mol Biol & Genet, Jeonju 54896, South Korea
[5] Chonnam Techno Coll, Dept Nursing, Chungnam 57500, South Korea
[6] RDA, Natl Inst Anim Sci, Grassland & Forage Div, Cheonan 31002, South Korea
基金
新加坡国家研究基金会;
关键词
H2O2; N-acetyl cysteine; Nrf2; Osteoblast differentiation; Oxidative stress; OSTEOBLASTIC DIFFERENTIATION; OXIDATIVE STRESS; BONE LOSS; RADIATION; PROTECTS; SYSTEM; HO-1;
D O I
10.5483/BMBRep.2015.48.11.112
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
There are controversial findings regarding the roles of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway on bone metabolism under oxidative stress. We investigated how Nrf2/HO-1 pathway affects osteoblast differentiation of MC3T3-E1 cells in response to hydrogen peroxide (H2O2), N-acetyl cysteine (NAC), or both. Exposing the cells to H2O2 decreased the alkaline phosphatase activity, calcium accumulation, and expression of osteoblast markers, such as osteocalcin and runt-related transcription factor-2. In contrast, H2O2 treatment increased the expression of Nrf2 and HO-1 in the cells. Treatment with hemin, a chemical HO-1 inducer, mimicked the inhibitory effect of H2O2 on osteoblast differentiation by increasing the HO-1 expression and decreasing the osteogenic marker genes. Pretreatment with NAC restored all changes induced by H2O2 to near normal levels in the cells. Collectively, our findings suggest that H2O2-mediated activation of Nrf2/HO-1 pathway negatively regulates the osteoblast differentiation, which is inhibited by NAC.
引用
收藏
页码:636 / 641
页数:6
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