Hydrogen Peroxide Induces G2 Cell Cycle Arrest and Inhibits Cell Proliferation in Osteoblasts
Hydrogen Peroxide Induces G2 Cell Cycle Arrest and Inhibits Cell Proliferation in Osteoblasts
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过氧化氢诱导 G2 细胞周期停滞并抑制成骨细胞的细胞增殖
DOI：
10.1002/ar.20925
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发表时间：
2009-08-01
影响因子：
2
通讯作者：
Bai, Xiao-Chun
中科院分区：
文献类型：
--
作者：
Li, Ming;Zhao, Li;Bai, Xiao-Chun
活性氧通过抑制成骨细胞分化和刺激破骨细胞生成参与骨质疏松症的发生。目前对ROS在成骨细胞增殖中的作用及如何调控成骨细胞增殖知之甚少。哺乳动物雷帕霉素靶蛋白mTOR是细胞生长和增殖的中心调节因子。在这里，我们报告的第一次，5200 μ M的过氧化氢（H2 O2）的剂量和时间依赖性抑制细胞增殖，而不影响细胞活力在小鼠成骨细胞系，MC 3 T3-E1，和人成骨细胞样细胞系，MG 63。进一步的研究表明，200 μ M的H_2O_2处理2- 4 -72小时，细胞周期蛋白B_1的蛋白水平明显下降，G（2）/M期细胞的比例增加2-4倍，0.5-5 mM的H_2O_2对细胞周期蛋白B_1的表达无明显影响，但对细胞周期蛋白B_1的表达无明显影响H2 O2（5-200 μ M）抑制mTOR信号传导，表现为MC 3 T3-E1和MG 63细胞中S6 K（T389）、4 E-BP 1（T37/46）和S6（S235/236）的去磷酸化。雷帕霉素可以抑制mTOR信号传导和细胞增殖，但不会降低细胞周期蛋白B1的蛋白水平。综上所述，H2 O2通过下调cyclin B1和诱导G（2）细胞周期阻滞抑制成骨细胞增殖。H2 O2对mTOR信号传导的抑制可能不参与该过程。Anat Rec，292：1107-1113，2009. (C)2009 Wiley-Liss，Inc.
Reactive oxygen species (ROSs) are involved in osteoporosis by inhibiting osteoblastic differentiation and stimulating osteoclastgenesis. Little is known about the role and how ROS controls proliferation of osteoblasts. Mammalian target of rapamycin, mTOR, is a central regulator of cell growth and proliferation. Here, we report for the first time that 5200 mu M hydrogen peroxide (H2O2) dose- and time-dependently suppressed cell proliferation without affecting cell viability in mouse osteoblast cell line, MC3T3-E1, and in human osteoblast-like cell line, MG63. Further study revealed that protein level of cyclin B1 decreased markedly and the percentage of the cells in G(2)/M phase increased about 2-4 fold by 200 mu M H2O2 treatment for 24-72 hr. A total of 0.5-5 mM of H2O2 but not lower concentrations (5-200 mu M) of H2O2 inhibited mTOR signaling, as manifested by dephosphorylation of S6K (T389), 4E-BP1 (T37/46), and S6(S235/236) in MC3T3-E1 and MG63 cells. Rapamycin, which could inhibit mTOR signaling and cell proliferation, however, did not reduce the protein level of cyclin B1. In a summary, H2O2 prevents cell proliferation of osteoblasts by down-regulating cyclin B1 and inducing G(2) cell cycle arrest. Inhibition of mTOR signaling by H2O2 may not be involved in this process. Anat Rec, 292:1107-1113, 2009. (C) 2009 Wiley-Liss, Inc.