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Bioengineering (Basel). 2017 Jun 15;4(2). pii: E56. doi: 10.3390/bioengineering4020056.

Three-Dimensional Culture Model of Skeletal Muscle Tissue with Atrophy Induced by Dexamethasone.

Author information

1
Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan. shimizu@chembio.nagoya-u.ac.jp.
2
Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan. genma.riho@k.mbox.nagoya-u.ac.jp.
3
Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan. gotou.yuuki@a.mbox.nagoya-u.ac.jp.
4
Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan. nagasaka.sumire@f.mbox.nagoya-u.ac.jp.
5
Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan. honda@chembio.nagoya-u.ac.jp.
6
Innovative Research Center for Preventive Medical Engineering, Nagoya University, Nagoya 464-8601, Japan. honda@chembio.nagoya-u.ac.jp.

Abstract

Drug screening systems for muscle atrophy based on the contractile force of cultured skeletal muscle tissues are required for the development of preventive or therapeutic drugs for atrophy. This study aims to develop a muscle atrophy model by inducing atrophy in normal muscle tissues constructed on microdevices capable of measuring the contractile force and to verify if this model is suitable for drug screening using the contractile force as an index. Tissue engineered skeletal muscles containing striated myotubes were prepared on the microdevices for the study. The addition of 100 µM dexamethasone (Dex), which is used as a muscle atrophy inducer, for 24 h reduced the contractile force significantly. An increase in the expression of Atrogin-1 and MuRF-1 in the tissues treated with Dex was established. A decrease in the number of striated myotubes was also observed in the tissues treated with Dex. Treatment with 8 ng/mL Insulin-like Growth Factor (IGF-I) for 24 h significantly increased the contractile force of the Dex-induced atrophic tissues. The same treatment, though, had no impact on the force of the normal tissues. Thus, it is envisaged that the atrophic skeletal muscle tissues induced by Dex can be used for drug screening against atrophy.

KEYWORDS:

cell-based assay; contractile force; disease model; drug screening; microdevice

Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript, or decision to publish the results.

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