CuZn-SOD欠損は低骨代謝回転型骨量減少と加齢性コラーゲン架橋変化を引き起こし骨脆弱化する CuZn-SOD Deficiency Causes Bone Fragility Due to Low Turnover Osteoporosis and Impaired Collagen Cross-linking

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<tt>The aging process correlates with the accumulation of cellular and tissue damage caused by oxidative stress. Although previous studies have suggested that oxidative stress plays a pathological role in the development of bone fragility, little direct evidence has been found. In order to investigate the pathological significance of oxidative stress in bones, we analyzed the bone tissue of mice deficient in cytoplasmic copper/zinc superoxide dismutase (CuZn-SOD, encoded by the </tt><tt><i>Sod1 </i></tt><tt>gene; </tt><tt><i>Sod1</i></tt><tt><sup><i>-/-</i></sup></tt><tt>). In the present study, we showed for the first time that </tt><tt><i>in vivo </i></tt><tt>cytoplasmic superoxide caused a distinct weakness in bone stiffness, decreased bone mineral density, aging-like changes in collagen cross-linking, and transcriptional alterations in the genes associated with osteogensis. We also showed that the surface areas of osteoblasts and osteoclasts were significantly decreased in the lumbar vertebrae of </tt><tt><i>Sod1</i></tt><tt><sup><i>-/- </i></sup></tt><tt>mice, indicating the occurrence of low turnover osteopenia. </tt><tt><i>In vitro </i></tt><tt>experiments demonstrated that intracellular oxidative stress induced cell death and reduced the proliferation in primary osteoblasts but not in osteoclasts, indicating that impaired osteoblast viability caused the decrease in the osteoblast number and suppressed RANKL/M-CSF osteoclastgenic signaling in bone. Furthermore, treatment with an antioxidant, vitamin C, effectively improved bone fragility and osteoblastic survival. These results imply that intracellular redox imbalance caused by SOD1 deficiency plays a pivotal role in the development and progression of bone fragility both </tt><tt><i>in vivo </i></tt><tt>and </tt><tt><i>in vitro</i></tt><tt>. We herein present a valuable model for investigating the effects of oxidative stress on bone fragility in order to develop suitable </tt><tt>therapeutic interventions.</tt>

収録刊行物

  • Biomedical research on trace elements

    Biomedical research on trace elements 23(1), 1-5, 2012-04-27

    Japan Society for Biomedical Research on Trace Elements

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各種コード

  • NII論文ID(NAID)
    10030755992
  • NII書誌ID(NCID)
    AN10423256
  • 本文言語コード
    JPN
  • 資料種別
    REV
  • ISSN
    0916717X
  • NDL 記事登録ID
    023760659
  • NDL 請求記号
    Z19-3255
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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