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

Kazunori Shimizu,Hiroyuki Honda,Riho Genma,Yuuki Gotou,Sumire Nagasaka

doi:10.3390/bioengineering4020056

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.

Highlights

Skeletal muscle atrophy and muscle mass loss weaken muscular strength, resulting in impairment of capacity for physical exercise
Skeletal muscle atrophy includes disuse muscle atrophy caused by a lack of physical exercise, being bedridden, sarcopenia due to aging, cachexia caused by cancer, and steroid myopathy due to excessive glucocorticoid presence [1,2,3]
ConInclaudsdioitniosn, variations in the expression levels of atrogenes in Dex and Dex + insulin-like growth factor -I (IGF-I) were examined (FiguTrheis5sBt)u. dTyhereepxoprrtesstshieondelevveelol pomf eeancthogf eanme uinscDleeaxtr+opIGhFy-mI wodaeslsbigyniinfidcuancitnlyg laotwroeprhcyominpnaorremdatlo mthuastcilne tDisesxue(Actornogstinru-1c:te3d.8o3n±a0m.3i9crfoodr eDveicxeacnadpa2b.8l9e ±of 0m.2e0asfourriDngexco+nItGraFc-tIi;leMfuorRcFe-.1T: h2e.7a9d±di0ti.o6n8 foofr Dex, used as an atrophy inducer in this study, to the tissues increases the expression of atrogenes

Summary

Introduction

Skeletal muscle atrophy and muscle mass loss weaken muscular strength, resulting in impairment of capacity for physical exercise. Skeletal muscles account for approximately half of the total body weight of adults and are the organs involved in motion and posture maintenance. They play a crucial role in energy production and carbohydrate metabolism. The functional deterioration of skeletal muscles directly causes a reduction in exercise capacity as well as a metabolic abnormality, in turn deteriorating the quality of life significantly. Because of the non-availability of a fundamental treatment for muscle atrophy, prevention and treatment by counter-measure therapies involving proper diet and exercise are performed [4,5]. The development of direct preventive/therapeutic drugs to counter muscle atrophy is urgently required

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