ID 111062
著者
Bayarsaikhan, Od Tokushima University
キーワード
myostatin
small-interfering RNAs
activin type IIB receptor
muscle hypertrophy
資料タイプ
学術雑誌論文
抄録
Background: Myostatin (Mstn) is a secreted TGF-β family member that controls skeletal muscle growth, 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 combinative effects of myostatin-targeting siRNA (Mstn-siRNA) and ActRIIB-Fc on murine myoblast in vitro and in vivo.
Materials and Methods: C2C12 cells were treated by Mstn-siRNA with or without ActRIIB-Fc at 0 and 48 h after differentiation. Myotube size was measured, and gene expression of Mstn, MuRF-1, MyoD and myogenin were analyzed. Furthermore, 11-week-old, male C57BL/6 mice were injected with atelocollagen (ATCOL)-mediated Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc locally into the masseter muscle twice a week. Histological and biochemical analyses were performed using the dissected muscles.
Results: Transfection of Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc resulted in significant increases in the myotube diameter of the C2C12 cells compared with untreated control. Also, treatment with Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc could lead to an upregulation of MyoD and myogenin gene expression and downregulation of Mstn and MuRF-1. In vivo, muscle fibril hypertrophy was observed in both Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc treated groups. Moreover, western blotting analysis showed that the p-Smad2/3 expression level was decreased by treatment of Mstn-siRNA/ActRIIB-Fc. In contrast, MyoD and myogenin protein levels were increased by combined treatment, compared with the other groups.
Conclusions: These suggest that double inhibition of myostain is potentially useful for myogenesis and muscle growth promotion. This may be a good as new treatment remedy for patients with various muscle atrophies, including muscular dystrophy.
掲載誌名
Journal of Oral Health and Biosciences
ISSN
21896682
出版者
四国歯学会
30
1
開始ページ
1
終了ページ
7
並び順
1
発行日
2017-06-30
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
歯学系
病院
医学系