SATB2 participates in regulation of menadione-induced apoptotic insults to osteoblasts

Jyh Ding Wei, Yi Ling Lin, Cheng Hsiu Tsai, Hui Shan Shieh, Pei I. Lin, Wei Pin Ho, Ruei Ming Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1058-1066
Number of pages9
JournalJournal of Orthopaedic Research
Volume30
Issue number7
DOIs
Publication statusPublished - Jul 2012

Keywords

  • apoptosis
  • menadione
  • mitochondria
  • osteoblasts
  • SATB2

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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