N-acetylcysteine stimulates osteoblastic differentiation of mouse calvarial cells
N-acetylcysteine stimulates osteoblastic differentiation of mouse calvarial cells
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DOI：
10.1002/jcb.21508
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发表时间：
2008-03-01
影响因子：
4
通讯作者：
Baek, Jeong-Hwa
中科院分区：
文献类型：
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作者：
Jun, Ji Hae;Lee, Sun-Hwan;Baek, Jeong-Hwa
雌激素缺乏通过增加活性氧（ROS）的产生引起骨质疏松症，因此，抗氧化剂可能被证明是有效的治疗候选者。我们研究了抗氧化剂N-乙酰半胱氨酸（NAC）对小鼠颅骨细胞成骨细胞分化的影响。NAC（10-30 mM）增强碱性磷酸酶活性，成骨细胞分化相关基因的mRNA表达和矿化结节形成。它还增加了骨形态发生蛋白-2，-4和-7的表达。NAC的成骨活性通过抑制谷胱甘肽合成而部分降低。由于咖啡酸苯乙酯不刺激成骨细胞分化，因此NAC的ROS清除活性不太可能足以产生成骨活性。我们观察到，NAC抑制小GTdR RhoA活性，并且多杀性巴氏杆菌毒素对RhoA的激活抑制NAC的成骨活性。这些结果表明，NAC可能通过增加谷胱甘肽合成和抑制RhoA活化来发挥其成骨活性。
Estrogen deficiency causes osteoporosis via increased generation of reactive oxygen species (ROS), and thus, antioxidants may prove to be the effective therapeutic candidates. We examined the effects of the antioxidant N-acetylcysteine (NAC) on osteoblastic differentiation in mouse calvarial cells. NAC (10-30 mM) enhanced alkaline phosphatase activity, mRNA expression of osteoblast differentiation-associated genes and mineralized nodule formation. It also increased expression of bone morphogenetic proteins-2, -4, and -7. The osteogenic activity of NAC was partially reduced by inhibition of glutathione synthesis. Since caffeic acid phenethyl ester did not stimulate osteoblast differentiation, it is unlikely that ROS scavenging activity of NAC is sufficient for osteogenic activity. We observed that NAC suppressed small GTPase RhoA activity and activation of RhoA by Pasteurella multocida toxin suppressed the osteogenic activity of NAC. These results suggest that NAC might exert its osteogenic activity via increased glutathione synthesis and inhibition of RhoA activation.