Co-administration of myostatin-targeting siRNA and ActRIIB-Fc fusion protein increases masseter muscle mass and fiber size
- Author:
Od Bayarsailhan
1
;
NOBUHIKO KAWAI
1
;
HIROYO MORI
1
;
NAO KINOUCHI
1
;
TAKESHI NIKAWA
1
;
EIJI TANAKA
1
Author Information
1. Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Sciences
- Publication Type:Journal Article
- Keywords:
Myostatin, treatment atrophic myopathy, fiber size
- From:Innovation
2018;12(4):53-
- CountryMongolia
- Language:Mongolian
-
Abstract:
Myostatin, a member of the TGF-beta 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-beta 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.
