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SATB2 participates in regulation of menadione‐induced apoptotic insults to osteoblasts
Author(s) -
Wei JyhDing,
Lin YiLing,
Tsai ChengHsiu,
Shieh HuiShan,
Lin PeiI,
Ho WeiPin,
Chen RueiMing
Publication year - 2012
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22046
Subject(s) - menadione , microbiology and biotechnology , oxidative stress , apoptosis , osteoblast , biology , chemistry , biochemistry , in vitro
Abstract Special AT‐rich sequence binding protein 2 (SATB2), a nuclear matrix attachment region‐binding protein, can regulate embryonic development, cell differentiation, and cell survival. Previous studies showed that SATB2 is involved in osteoblast differentiation and skeletal development. In this study, we evaluated the role of SATB2 in oxidative stress‐induced apoptotic insults to human osteoblast‐like MG63 cells and mouse MC3T3‐E1 cells. Exposure of MG63 cells to menadione increased intracellular reactive oxygen species levels in a concentration‐ and time‐dependent manner. Simultaneously, menadione‐induced oxidative stress triggered cell shrinkage and decreased cell viability. In addition, treatment of MG63 cells with menadione time‐dependently decreased the mitochondrial membrane potential but enhanced caspase‐3 activity. As a result, menadione‐induced DNA fragmentation and cell apoptosis. As to the mechanism, exposure of MG63 cells to menadione amplified SATB2 messenger (m)RNA and protein expression in a time‐dependent manner. Knockdown of translation of SATB2 mRNA using RNA interference led to chromatin disruption and nuclear damage. When MG63 cells and MC3T3‐E1 cells were treated with SATB2 small interfering RNA, menadione‐induced cell apoptosis was increased. We conclude that menadione causes oxidative stress in human osteoblasts and induces cellular apoptosis via a mitochondrion‐caspase protease pathway. In addition, SATB2 may play a crucial role in protecting against oxidative stress‐induced osteoblast apoptosis. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1058–1066, 2012