<i>N</i>‐acetylcysteine stimulates osteoblastic differentiation of mouse calvarial cells

Jun, Ji Hae; Lee, Sun-Hwan; Kwak, Han Bok; Lee, Zang Hee; Seo, Sang-Beum; Woo, Kyung Mi; Ryoo, Hyun‐Mo; Kim, Gwan-Shik; Baek, Jeong‐Hwa

doi:10.1002/jcb.21508

Cited by 69 publications

(60 citation statements)

References 35 publications

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“…These events increase bone remodeling turnover with consequent alteration and decrease in bone mass. Antioxidants have opposing effects, they contribute to the differentiation of osteoblasts and bone formation (8,15,34,47), maintaining vital osteocytes which contribute to osteoblast activity and osteogenesis, while reduce the osteoclast differentiation and their activity ( Figure 1). There are several factors mainly produced by osteoblasts and osteocytes that regulate osteoclast and osteoblast activity and then bone remodeling, among these the most important are: the ligand of receptor activator of NF-kB (RANKL) and osteoprotegerin (OPG).…”

Section: Oxidative Stress In Bone Remodelingmentioning

confidence: 99%

“…All these antioxidants act as direct scavengers of ROS, but they also maintain high levels of GSH, in fact, together with GSH-reductase they contribute to the elimination of GSSG formed in the reduction reactions, maintaining normal levels of GSH/GSSG and the intracellular redox state (8,14,47). Some studies relate antioxidants to bone metabolism, in fact a marked decrease in plasma antioxidants was found in aged or osteoporotic rats and in aged or osteoporotic women (17,19,38).…”

Section: Antioxidants In Bone Remodeling and In Bone Lossmentioning

confidence: 99%

“…As regards thiol antioxidants some data have been obtained by using NAC, GSH and LA. NAC, a cysteine analogue drug with many therapeutic applications, has a protective role in controlling oxidative stress against many cells including osteoblasts, and stimulates osteoblastic differentiation of mouse calvarial cells (8,14,47,62). Other studies report that NAC inhibits oxidative stress induced apoptosis of osteoblastic cells, and this is mediated by GSH (63,64), moreover, NAC prevents osteoclast formation, NF-κB activation and TNF-α expression involved in osteoclast activation (49).…”

Section: Antioxidants In Bone Remodeling and In Bone Lossmentioning

confidence: 99%

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Oxidative stress in bone remodeling: role of antioxidants

Domazetovic

Marcucci

Iantomasi

et al. 2017

ccmbm

544

524

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SummaryROS are highly reactive molecules which consist of a number of diverse chemical species, including radical and non-radical oxygen species. Oxidative stress occurs as a result of an overproduction of ROS not balanced by an adequate level of antioxidants. The natural antioxidants are: thiol compounds among which GSH is the most representative, and non-thiol compounds such as polyphenols, vitamins and also various enzymes. Many diseases have been linked to oxidative stress including bone diseases among which one of the most important is the osteoporosis. The redox state changes are also related to the bone remodeling process which allows the continuous bone regeneration through the coordinated action of bone cells: osteoclasts, osteoblasts and osteocytes. Changes in ROS and/or antioxidant systems seem to be involved in the pathogenesis of bone loss. ROS induce the apoptosis of osteoblasts and osteocytes, and this favours osteoclastogenesis and inhibits the mineralization and osteogenesis. Excessive osteocyte apoptosis correlates with oxidative stress causing an imbalance in favor of osteoclastogenesis which leads to increased turnover of bone remodeling and bone loss. Antioxidants either directly or by counteracting the action of oxidants contribute to activate the differentiation of osteoblasts, mineralization process and the reduction of osteoclast activity. In fact, a marked decrease in plasma antioxidants was found in aged or osteoporotic women. Some evidence shows a link among nutrients, antioxidant intake and bone health. Recent data demonstrate the antioxidant properties of various nutrients and their influence on bone metabolism. Polyphenols and anthocyanins are the most abundant antioxidants in the diet, and nutritional approaches to antioxidant strategies, in animals or selected groups of patients with osteoporosis or inflammatory bone diseases, suggest the antioxidant use in anti-resorptive therapies for the treatment and prevention of bone loss.

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Section: Oxidative Stress In Bone Remodelingmentioning

confidence: 99%

Section: Antioxidants In Bone Remodeling and In Bone Lossmentioning

confidence: 99%

Section: Antioxidants In Bone Remodeling and In Bone Lossmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative stress in bone remodeling: role of antioxidants

Domazetovic

Marcucci

Iantomasi

et al. 2017

ccmbm

544

524

View full text Add to dashboard Cite

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“…However, the protective properties of NAC should be carefully analyzed, because NAC itself enhances the osteoblastic differentiation of mouse calvarial cells. 12 Because other antioxidants, such…”

Section: Introductionmentioning

confidence: 99%

Effects of N‐acetylcysteine on TEGDMA‐ and HEMA‐induced suppression of osteogenic differentiation of human osteosarcoma MG63 cells

et al. 2011

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Triethyleneglycol dimethacrylate (TEGDMA) and 2-hydroxyethyl methacrylate (HEMA) are major resinous components of dental restorative materials and dentin bonding adhesives. Resin monomers are known to cause cytotoxicity in mammalian cells via oxidative stress and inhibit differentiation of dental pulp cells and osteoblasts. This study was aimed to investigate whether oxidative stress was involved in the inhibition of TEGDMA- and HEMA-induced differentiation. TEGDMA and HEMA reduced alkaline phosphatase (ALP) activity and the mRNA expression of the osteopontin (OPN) gene in MG63 cells at noncytotoxic concentrations. On the other hand, N-acetylcysteine (NAC) did not affect ALP activity at concentrations below 10 mM. Reduced ALP activity and OPN mRNA expression by TEGDMA were partially recovered via cotreatment with NAC. However, NAC did not exhibit significant effects in HEMA-treated cells. Glutathione (GSH) levels were also down-regulated by both TEGDMA and HEMA. The addition of NAC induced the partial recovery of GSH in cells treated with 0.5 mM TEGDMA. On the other hand, the levels of GSH in HEMA-treated cells were not affected by NAC. These results suggest that oxidative stress is involved in the suppression of differentiation by TEGDMA. Translocation of Nrf2 from the cytoplasm to the nucleus has been known to play a role in the suppression of osteogenic differentiation by oxidative stress. However, Nrf2 did not move into the nucleus in resin monomer-treated MG63 cells, suggesting the contribution of other signaling pathways to the suppressive effects of resin monomers.

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“…Interest in NAC has increased because of its ability to inhibit synthesis of pro-inflammatory molecules and to enhance the immune functions of phagocytes and lymphocytes (Victor et al, 2003;Winyard and Blake, 1997). Studies have also demonstrated that NAC suppresses osteoclast differentiation and stimulates osteoblast differentiation (Jun et al, 2008;Lee et al, 2005). Furthermore, NAC has been shown to inhibit the expression of lipopolysaccharide-induced inflammatory mediators in gingival fibroblasts and suppress alveolar bone loss in an experimental periodontitis model in rats (Kim et al, 2007;Toker et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Antioxidants on the Production of Pro-Inflammatory Cytokines and Orthodontic Tooth Movement

Chae

Park

Hwang

et al. 2011

Molecules and Cells

Self Cite

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Orthodontic force causes gradual compression of the periodontal ligament tissues, which leads to local hypoxia in the compression side of the tissues. In this study, we investigated whether antioxidants exert a regulatory effect on two factors: the expression of pro-inflammatory cytokines in human periodontal ligament fibroblasts (PDLFs) that were exposed to mechanical compression and hypoxia and the rate of orthodontic tooth movement in rats. Exposure of PDLFs to mechanical compression (0.5-3.0 g/cm 2 ) or hypoxic conditions increased the production of intracellular reactive oxygen species. Hypoxic treatment for 24 h increased the mRNA levels of IL-1β, IL-6 and IL-8 as well as vascular endothelial growth factor (VEGF) in PDLFs. Resveratrol (10 nM) or N-acetylcysteine (NAC, 20 mM) diminished the transcriptional activity of hypoxiainducible factor-1 and hypoxia-induced expression of VEGF. Combined treatment with mechanical compression and hypoxia significantly increased the expression levels of IL-1β, IL-6, IL-8, TNF-α and VEGF in PDLFs. These levels were suppressed by NAC and resveratrol. The maxillary first molars of rats were moved mesially for seven days using an orthodontic appliance. NAC decreased the amount of orthodontic tooth movement compared to the vehicletreated group. The results from immunohistochemical staining demonstrated that NAC suppressed the expression of IL-1β and TNF-α in the periodontal ligament tissues compared to the vehicle-treated group. These results suggest that antioxidants have the potential to negatively regulate the rate of orthodontic tooth movement through the down-regulation of pro-inflammatory cytokines in the compression sides of periodontal ligament tissues.

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N‐acetylcysteine stimulates osteoblastic differentiation of mouse calvarial cells

Cited by 69 publications

References 35 publications

Oxidative stress in bone remodeling: role of antioxidants

Oxidative stress in bone remodeling: role of antioxidants

Effects of N‐acetylcysteine on TEGDMA‐ and HEMA‐induced suppression of osteogenic differentiation of human osteosarcoma MG63 cells

The Effect of Antioxidants on the Production of Pro-Inflammatory Cytokines and Orthodontic Tooth Movement

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