Co-Administration of Myostatin-Targeting siRNA and ActRIIB-Fc Fusion Protein Increases Masseter Muscle Mass and Fiber Size

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Author(s)

    • KAWAI Nobuhiko KAWAI Nobuhiko
    • Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School|Department of Nutritional Physiology, Institute of Biomedical Sciences, Tokushima University Graduate School
    • MORI Hiroyo MORI Hiroyo
    • Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School
    • KINOUCHI Nao KINOUCHI Nao
    • Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School
    • TANAKA Eiji TANAKA Eiji
    • Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School

Abstract

Myostatin, a member of the TGF-β superfamily, is a negative regulator of skeletal muscle cell growth and differentiation, and binds with high affinity to the activin type IIB receptor (ActRIIB). The soluble ligand-binding domain of ActRIIB fused to the Fc domain of IgG (ActRIIB-Fc) potently binds and inhibits TGF-β family members in muscle, leading to rapid and marked muscle growth. The present study was designed to assess the effectiveness of the co-delivery of myostatin-targeting siRNA (Mstn-siRNA) and ActRIIB-Fc into skeletal muscle as a potential treatment of atrophic myopathies. Eleven-week-old, male C57BL/6 mice were injected with atelocollagen (ATCOL)-mediated Mstn-siRNA with/without ActRIIB-Fc locally into the masseter muscle twice a week. Inhibition of myostatin function by the combination of Mstn-siRNA and ActRIIB-Fc increased muscle weight and myofibril size in murine masseter muscle. Real-time RT-PCR analysis revealed significant downregulation of myostatin mRNA expression in both the Mstn-siRNA-treated and the combination treatment group. Furthermore, myogenin mRNA expression was upregulated in the combination treatment group, while MuRF-1 and Atrogin-1 mRNA expression was downregulated compared to administration of each compound alone. These findings suggest that double inhibition of myostatin is a potentially useful treatment strategy to increase muscle mass and fiber size and could be a useful treatment of patients with various muscle atrophies, including muscular dystrophy.

Journal

  • Journal of Nutritional Science and Vitaminology

    Journal of Nutritional Science and Vitaminology 63(4), 244-248, 2017

    The Vitamin Society of Japan|Japan Society of Nutrition and Food Science|Center for Academic Publications Japan

Codes

  • NII Article ID (NAID)
    130007314434
  • NII NACSIS-CAT ID (NCID)
    AA00703822
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    0301-4800
  • NDL Article ID
    028470821
  • NDL Call No.
    Z53-B484
  • Data Source
    NDL  IR  J-STAGE 
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