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N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway
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  • Journal title : BMB Reports
  • Volume 48, Issue 11,  2015, pp.636-641
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2015.48.11.112
 Title & Authors
N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway
Lee, Daewoo; Kook, Sung-Ho; Ji, Hyeok; Lee, Seung-Ah; Choi, Ki-Choon; Lee, Kyung-Yeol; Lee, Jeong-Chae;
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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.
H2O2;N-acetyl cysteine;Nrf2;Osteoblast differentiation;Oxidative stress;
 Cited by
Mody N, Parhami F, Sarafian TA and Demer LL (2001) Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med 31, 509-519 crossref(new window)

Bai XC, Lu D, Bai J et al (2004) Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB. Biochem Biophys Res Commun 314, 197-207 crossref(new window)

Kondo H, Yumoto K, Alwood JS et al (2010) Oxidative stress and gamma radiation-induced cancellous bone loss with musculoskeletal disuse. J Appl Physiol (1985) 108, 152-161 crossref(new window)

Banfi G, Iorio EL and Corsi MM (2008) Oxidative stress, free radicals and bone remodeling. Clin Chem Lab Med 46, 1550-1555

Jia P, Xu YJ, Zhang ZL et al (2012) Ferric ion could facilitate osteoclast differentiation and bone resorption through the production of reactive oxygen species. J Orthop Res 30, 1843-1852 crossref(new window)

Ueno T, Yamada M, Igarashi Y and Ogawa T (2011) N-acetyl cysteine protects osteoblastic function from oxidative stress. J Biomed Mater Res A 99, 523-531 crossref(new window)

Singh PK, Wise SY, Ducey EJ, Fatanmi OO, Elliott TB and Singh VK (2012) α-Tocopherol succinate protects mice against radiation-induced gastrointestinal injury. Radiat Res 177, 133-145 crossref(new window)

Zhang Q, Pi J, Woods CG and Andersen ME (2010) A systems biology perspective on Nrf2-mediated antioxidant response. Toxicol Appl Pharmacol 244, 84-97 crossref(new window)

Shin SM, Yang JH and Ki SH (2013) Role of the Nrf2-ARE pathway in liver diseases. Oxid Med Cell Longev 2013, 763257 crossref(new window)

Maines MD and Panahian N (2001) The heme oxygenase system and cellular defense mechanisms. Do HO-1 and HO-2 have different functions? Adv Exp Med Biol 502, 249-272 crossref(new window)

Zwerina J, Tzima S, Hayer S et al (2005) Heme oxygenase 1 (HO-1) regulates osteoclastogenesis and bone resorption. FASEB J 19, 2011-2013

Chen JS, Huang PH, Wang CH et al (2011) Nrf-2 mediated heme oxygenase-1 expression, an antioxidant-independent mechanism, contributes to anti-atherogenesis and vascular protective effects of Ginkgo biloba extract. Atherosclerosis 214, 301-309 crossref(new window)

Rana T, Schultz MA, Freeman ML and Biswas S (2012) Loss of Nrf2 accelerates ionizing radiation-induced bone loss by upregulating RANKL. Free Radic Biol Med 53, 2298-2307 crossref(new window)

Yu J, Zhu X, Qi X, Che J and Cao B (2013) Paeoniflorin protects human EA.hy926 endothelial cells against gamma- radiation induced oxidative injury by activating the NF-E2-related factor 2/heme oxygenase-1 pathway. Toxicol Lett 218, 224-234 crossref(new window)

Hinoi E, Fujimori S, Wang L, Hojo H, Uno K and Yoneda Y (2006) Nrf2 negatively regulates osteoblast differentiation via interfering with Runx2-dependent transcriptional activation. J Biol Chem 281, 18015-18024 crossref(new window)

Lin TH, Tang CH, Hung SY et al (2010) Upregulation of heme oxygenase-1 inhibits the maturation and mineralization of osteoblasts. J Cell Physiol 222, 757-768

Lee JH and Cho JY (2014) Proteomics approaches for the studies of bone metabolism. BMB Rep 47, 141-148 crossref(new window)

Neve A, Corrado A and Cantatore FP (2013) Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol 228, 1149-1153 crossref(new window)

Jun JH, Lee SH, Kwak HB et al (2008) N-acetyl cysteine stimulates osteoblastic differentiation of mouse calvarial cells. J Cell Biochem 103, 1246-1255 crossref(new window)

Kim KA, Kook SH, Song JH and Lee JC (2014) A phenolic acid phenethyl urea derivative protects against irradiation- induced osteoblast damage by modulating intracellular redox state. J Cell Biochem 115, 1877-1887

Arai M, Shibata Y, Pugdee K, Abiko Y and Ogata Y (2007) Effects of reactive oxygen species (ROS) on antioxidant system and osteoblastic differentiation in MC3T3-E1 cells. IUBMB Life 59, 27-33 crossref(new window)

Ahanger AA, Prawez S, Leo MD et al (2010) Pro-healing potential of hemin: an inducer of heme oxygenase-1. Eur J Pharmacol 645, 165-170 crossref(new window)

Kook YA, Lee SK, Son DH et al (2009) Effects of substance P on osteoblastic differentiation and heme oxygenase-1 in human periodontal ligament cells. Cell Biol Int 33, 424-428 crossref(new window)

Kozakowska M, Szade K, Dulak J and Jozkowicz A (2013) Role of heme oxygenase-1 in postnatal differentiation of stem cells: a possible cross-talk with microRNAs. Antioxid Redox Signal 20, 1827-1850 crossref(new window)

Kim GY, Park SY, Jo A et al (2015) Gecko proteins induce the apoptosis of bladder cancer 5637 cell by inhibiting Akt and activating intrinsic caspase cascade. BMB Rep 48, 531-536 crossref(new window)

Park SS, Kim KA, Lee SY, Lim SS, Jeon YM and Lee JC (2012) X-ray radiation at low doses stimulates differentiation and mineralization of mouse calvarial osteoblasts. BMB Rep 45, 571-576 crossref(new window)

Heo JS, Lee SY and Lee JC (2010) Wnt/β-catenin signaling enhances osteoblastogenic differentiation from human periodontal ligament fibroblasts. Mol Cells 30, 449-454 crossref(new window)

Jeon YM, Kook SH, Rho SJ et al (2013) Fibroblast growth factor-7 facilitates osteogenic differentiation of embryonic stem cells through the activation of ERK/Runx2 signaling. Mol Cell Biochem 382, 37-45 crossref(new window)

Yu JY, Zheng ZH, Son YO, Shi X, Jang YO and Lee JC (2011) Mycotoxin zearalenone induces AIF- and ROSmediated cell death through p53- and MAPK-dependent signaling pathways in RAW264.7 macrophages. Toxicol In Vitro 25, 1654-1663 crossref(new window)