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ID 111062
Title Alternative
Myostatin-siRNAおよびActivinIIB型受容体融合タンパク質の共導入による骨格筋形成制御効果の検討
Author
Bayarsaikhan, Od Tokushima University
Keywords
myostatin
small-interfering RNAs
activin type IIB receptor
muscle hypertrophy
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Journal of Oral Health and Biosciences
ISSN
21896682
Publisher
四国歯学会
Volume
30
Issue
1
Start Page
1
End Page
7
Sort Key
1
Published Date
2017-06-30
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨:LID201704281013.pdf
審査要旨:LID201704281014.pdf
論文本文:k3085_fulltext.pdf
本論文は,著者Od BAYARSAIKHANの学位論文として提出され,学位審査・授与の対象となっている。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3085号
Diploma Number
甲口第428号
Granted Date
2017-03-23
Degree Name
Doctor of Dental Science
Grantor
Tokushima University
departments
Oral Sciences
University Hospital
Medical Sciences