Effects of reactive oxygen species (ROS) on antioxidant system and osteoblastic differentiation in MC3T3‐E1 cells

Arai, Masato; Shibata, Yasuko; Pugdee, Kamolparn; Abiko, Yoshimitsu; Ogata, Yorimasa

doi:10.1080/15216540601156188

Cited by 205 publications

(147 citation statements)

References 14 publications

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“…Thus, in development, developmental signaling may be regulated by the status of a specific redox couple and promote a specific cell type. In cellular models of osteogenesis, MC3T3-E1 differentiation was significantly decreased with prior subtoxic treatment of hydrogen peroxide, and mineralization was decreased by nearly half [18]. Markers of osteogenic differentiation, bone sialoprotein (BSP), osteocalcin (OS) and Runx2, were decreased as well, indicating a failure of cells to differentiate normally.…”

Section: Discussionmentioning

confidence: 92%

Differential redox potential profiles during adipogenesis and osteogenesis

Imhoff

Hansen

2011

Cellular and Molecular Biology Letters

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Development is an orderly process that requires the timely activation and/or deactivation of specific regulatory elements that control cellular proliferation, differentiation and apoptosis. While many studies have defined factors that control developmental signaling, the role of intracellular reduction/oxidation (redox) status as a means to control differentiation has not been fully studied. Redox states of intracellular couples may play a very important role in regulating redox-sensitive elements that are involved in differentiation signaling into specific phenotypes. In human mesenchymal stem cells (hMSCs), which are capable of differentiating into many different types of phenotypes, including osteoblasts and adipocytes, glutathione (GSH), cysteine (Cys) and thioredoxin-1 (Trx1) redox potentials were measured during adipogenesis and osteogenesis. GSH redox potentials (E h ) during both osteogenesis and adipogenesis became increasingly oxidized as differentiation ensued, but the rate at which this oxidation occurred was unique for each process. During adipogenesis, Cys E h became oxidized as adipogenesis progressed but during osteogenesis, it became reduced. Interestingly, intracellular Trx1 concentrations appeared to increase in both adipogenesis and osteogenesis, but the E h was unchanged when compared to undifferentiated hMSCs. These data show that hMSC differentiation into either adipocytes of osteoblasts corresponds to a unique redox state profile, suggesting that differentiation into specific phenotypes are likely regulated by redox states that are permissive to a specific developmental process.

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Section: Discussionmentioning

confidence: 92%

Differential redox potential profiles during adipogenesis and osteogenesis

Imhoff

Hansen

2011

Cellular and Molecular Biology Letters

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“…A recent study demonstrated that increased ROS generation, particularly H 2 O 2 , is predominately located around calcifying foci, which potentiates aortic valve calcification progression (54). By contrast, H 2 O 2 has been shown to have adverse effects on osteogenic differentiation of MC3T3-E1 cells, a pre-osteoblastic cell line (53), and primary bone marrow stromal cells and calvarial osteoblast precursors (55). Therefore, the effects of H 2 O 2 on osteogenic differentiation appear to be cell type-dependent.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress Induces Vascular Calcification through Modulation of the Osteogenic Transcription Factor Runx2 by AKT Signaling

Byon

Javed

Dai

et al. 2008

Journal of Biological Chemistry

556

537

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Oxidative stress plays a critical role in the pathogenesis of atherosclerosis including the formation of lipid laden macrophages and the development of inflammation. However, oxidative stress-induced molecular signaling that regulates the development of vascular calcification has not been investigated in depth. Osteogenic differentiation of vascular smooth muscle cells (VSMC) is critical in the development of calcification in atherosclerotic lesions. An important contributor to oxidative stress in atherosclerotic lesions is the formation of hydrogen peroxide from diverse sources in vascular cells. In this study we defined molecular signaling that is operative in the H 2 O 2 -induced VSMC calcification. We found that H 2 O 2 promotes a phenotypic switch of VSMC from contractile to osteogenic phenotype. This response was associated with an increased expression and transactivity of Runx2, a key transcription factor for osteogenic differentiation. The essential role of Runx2 in oxidative stress-induced VSMC calcification was further confirmed by Runx2 depletion and overexpression. Inhibition of Runx2 using short hairpin RNA blocked VSMC calcification, and adenovirus-mediated overexpression of Runx2 alone induced VSMC calcification. Inhibition of H 2 O 2 -activated AKT signaling blocked VSMC calcification and Runx2 induction concurrently. This blockage did not cause VSMC apoptosis. Taken together, our data demonstrate a critical role for AKT-mediated induction of Runx2 in oxidative stress-induced VSMC calcification.Atherosclerosis is characterized by the presence of atherosclerotic lesions in the arterial intima that leads to narrowing of the vessel lumen. Vascular calcification, the presence of calcium deposits in the vessel wall, is a feature of advanced atherosclerosis and reduces elasticity and compliance of the vessel wall (1). Hence, the extent of calcification is a key risk factor in the pathogenesis of the disease. Several cell types, such as endothelium, monocytes, and vascular smooth muscle cells (VSMC), 5 are involved in different stages of lesion development. VSMC contribute to the development of atherosclerotic lesions through increased migration, proliferation, secretion of matrix components, osteogenic differentiation, and the associated calcification (1). During this process, the differentiated VSMC undergo de-differentiation, and subsequently osteogenic transition that results in vascular calcification (2).Many factors that have been linked to an increased prevalence of vascular calcification are associated with elevated oxidative stress, including hypercholesterolemia, hypertension, diabetes mellitus, and dialysis-dependent end stage renal disease (3-6). Pro-oxidant events in atherosclerosis include the production of reactive oxygen species (ROS) and nitrogen species by vascular cells (7). Of particular interest is hydrogen peroxide (H 2 O 2 ), which is a cell-permeable ROS that has emerged as a key mediator of intracellular signaling (8 -10). H 2 O 2 is produced in vascular cells by multiple enzyma...

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“…Reduced bone mineral density involved a decrease in anti-oxidant defense and impairment of osteoblast maturation and mineralization (Mody et al, 2001;Maggio et al, 2003). Exposure of osteoblastic cells to hydrogen peroxide decreased mineralization and expression of Runx2, COL I, and ALP (Bai et al, 2004;Arai et al, 2007). Furthermore, N-acetylcysteine (NAC), a scavenger of ROS, protected pulp cells from PMMAinduced inhibition of ALP activity Yamada et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

TEGDMA Reduces Mineralization in Dental Pulp Cells

et al. 2010

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A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental. ABSTRACT Direct application of dentin bonding agents onto the exposed pulp has been advocated, but in vivo studies indicate a lack of reparative dentin formation. Our objective was to investigate the role of triethylene glycol dimethacrylate (TEGDMA), a commonly used compound in dentin bonding agents, as a potential inhibitor of mineralization. Human pulp cells were exposed to different concentrations of TEGDMA, and expression of the mineralization-related genes collagen I, alkaline phosphatase, bone sialoprotein, osteocalcin, Runx2, and dentin sialophosphoprotein was analyzed. Gene expression studies by real-time polymerase chain-reaction revealed a concentration-and timedependent decrease of mineralization markers. A subtoxic TEGDMA concentration (0.3 mM) reduced expression levels by 5 to 20% after 4 hrs and by 50% after 12 hrs. Furthermore, alkaline phosphatase activity and calcium deposition were significantly lower in dental pulp cells treated with TEGDMA over 14 days. These findings indicate that even low TEGDMA concentrations might inhibit mineralization induced by dental pulp cells, thus impairing reparative dentin formation after pulp capping with dentin bonding agents.

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Effects of reactive oxygen species (ROS) on antioxidant system and osteoblastic differentiation in MC3T3‐E1 cells

Cited by 205 publications

References 14 publications

Differential redox potential profiles during adipogenesis and osteogenesis

Differential redox potential profiles during adipogenesis and osteogenesis

Oxidative Stress Induces Vascular Calcification through Modulation of the Osteogenic Transcription Factor Runx2 by AKT Signaling

TEGDMA Reduces Mineralization in Dental Pulp Cells

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