Hydrogen Peroxide Induces G2 Cell Cycle Arrest and Inhibits Cell Proliferation in Osteoblasts

Authors

  • Ming Li,

    1. Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
    2. Institute of Orthopedics, Southern Medical University, Guangzhou, China
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  • Li Zhao,

    1. Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
    2. Institute of Orthopedics, Southern Medical University, Guangzhou, China
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  • Jun Liu,

    1. Department of Urology, Guangzhou General Hospital of Guangzhou Command, Guangzhou, China
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  • An-Ling Liu,

    1. Institute of Genetic Engineering, Southern Medical University, Guangzhou, China
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  • Wei-Sen Zeng,

    1. Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
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  • Shen-Qiu Luo,

    Corresponding author
    1. Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
    • Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
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    • Fax: 86-20-61648208

  • Xiao-Chun Bai

    Corresponding author
    1. Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
    2. Institute of Orthopedics, Southern Medical University, Guangzhou, China
    • Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
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Abstract

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 5–200 μM 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 G2/M phase increased about 2-4 fold by 200 μM H2O2 treatment for 24–72 hr. A total of 0.5–5 mM of H2O2 but not lower concentrations (5–200 μM) 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 G2 cell cycle arrest. Inhibition of mTOR signaling by H2O2 may not be involved in this process. Anat Rec, 292:1107–1113, 2009. © 2009 Wiley-Liss, Inc.

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