A novel in vitro model of sarcopenia using BubR1 hypomorphic C2C12 myoblasts

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• 作者：Takateru Nozaki ; Shiori Nikai ; Ryo Okabe ; Kiyoko Nagahama ; Nozomu Eto
• 关键词：Sarcopenia ; BubR1 hypomorphic C2C12 ; Myogenic differentiation ; Muscle ; specific ubiquitin ligases
• 刊名：Cytotechnology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：68
• 期：5
• 页码：1705-1715
• 全文大小：1,926 KB
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Biotechnology
  Biomedicine
  Biochemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-0778
• 卷排序：68

文摘

Sarcopenia is the age-related loss of skeletal muscle mass and function with adverse outcomes that include physical disability, poor quality of life, and death. The detailed molecular mechanisms remain unknown. An in vitro muscle atrophy model is needed to enable mechanistic studies. To create such a model, we employed BubR1 insufficiency which causes premature ageing in mice. Using C2C12 cells, a recognized in vitro model of the skeletal muscle cell, we obtained the BubR1 hypomorphic C2C12 (C2C12BKD) cells by using shRNA. The resulting C2C12BKD cells displayed several characteristics of the sarcopenic muscle cell. In C2C12BKD cells, formation of myotubes, assessed by analysis of fusion index, was markedly reduced as was the expression of myogenin and MyoD, two marker genes for myogenesis. Moreover, the cells showed increased expression of the muscle-specific ubiquitin ligases Atrogin-1 and MuRF-1, indicating increased protein degradation through the ubiquitin–proteasome dependent proteolytic pathway. These results suggest that C2C12BKD cells are potentially useful as a novel in vitro model of sarcopenia.