title: N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway.
abstract: 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.
authors: Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju 54896, Korea.
authors: Daewoo
authors: D
authors: Lee
authors: Institute of Oral Biosciences and School of Dentistry; Department of Bioactive Material Sciences and Institute of Molecular Biology and Genetics, Chonbuk National University, Jeonju 54896, Korea.
authors: Sung-Ho
authors: SH
authors: Kook
authors: Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju 54896, Korea.
authors: Hyeok
authors: H
authors: Ji
authors: Department of Nursing, Chonnam Techno College, Chonnam 57500, Korea.
authors: Seung-Ah
authors: SA
authors: Lee
authors: Grassland and Forage Division, National Institute of Animal Science, RDA, Cheonan 31002, Korea.
authors: Ki-Choon
authors: KC
authors: Choi
authors: Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju 54896, Korea.
authors: Kyung-Yeol
authors: KY
authors: Lee
authors: Institute of Oral Biosciences and School of Dentistry; Department of Bioactive Material Sciences and Institute of Molecular Biology and Genetics, Chonbuk National University, Jeonju 54896, Korea.
authors: Jeong-Chae
authors: JC
authors: Lee
mesh_terms: D016475:3T3 Cells; D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010006:Osteoblasts; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D051267:NF-E2-Related Factor 2; D015675:Osteocalcin; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D000111:Acetylcysteine