TY - JOUR
T1 - Conditional deletion of dicer in adult mice impairs skeletal muscle regeneration
AU - Oikawa, Satoshi
AU - Lee, Minjung
AU - Akimoto, Takayuki
N1 - Funding Information:
Funding: This research was supported, in part, by Grants-in-Aid for Young Investigators (A) (18680047 and 21680049 to T.A.) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. S. Oikawa was supported by the Japan Society for the Promotion of Science.
Funding Information:
This research was supported, in part, by Grants-in-Aid for Young Investigators (A) (18680047 and 21680049 to T.A.) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. S. Oikawa was supported by the Japan Society for the Promotion of Science. We thank Brian Harfe (University of Florida) for providing the Dicer1-floxed mice.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/11/2
Y1 - 2019/11/2
N2 - Skeletal muscle has a remarkable regenerative capacity, which is orchestrated by multiple processes, including the proliferation, fusion, and differentiation of the resident stem cells in muscle. MicroRNAs (miRNAs) are small noncoding RNAs that mediate the translational repression or degradation of mRNA to regulate diverse biological functions. Previous studies have suggested that several miRNAs play important roles in myoblast proliferation and differentiation in vitro. However, their potential roles in skeletal muscle regeneration in vivo have not been fully established. In this study, we generated a mouse in which the Dicer gene, which encodes an enzyme essential in miRNA processing, was knocked out in a tamoxifen-inducible way (iDicer KO mouse) and determined its regenerative potential after cardiotoxin-induced acute muscle injury. Dicer mRNA expression was significantly reduced in the tibialis anterior muscle of the iDicer KO mice, whereas the expression of muscle-enriched miRNAs was only slightly reduced in the Dicer-deficient muscles. After cardiotoxin injection, the iDicer KO mice showed impaired muscle regeneration. We also demonstrated that the number of PAX7+ cells, cell proliferation, and the myogenic differentiation capacity of the primary myoblasts did not differ between the wild-type and the iDicer KO mice. Taken together, these data demonstrate that Dicer is a critical factor for muscle regeneration in vivo.
AB - Skeletal muscle has a remarkable regenerative capacity, which is orchestrated by multiple processes, including the proliferation, fusion, and differentiation of the resident stem cells in muscle. MicroRNAs (miRNAs) are small noncoding RNAs that mediate the translational repression or degradation of mRNA to regulate diverse biological functions. Previous studies have suggested that several miRNAs play important roles in myoblast proliferation and differentiation in vitro. However, their potential roles in skeletal muscle regeneration in vivo have not been fully established. In this study, we generated a mouse in which the Dicer gene, which encodes an enzyme essential in miRNA processing, was knocked out in a tamoxifen-inducible way (iDicer KO mouse) and determined its regenerative potential after cardiotoxin-induced acute muscle injury. Dicer mRNA expression was significantly reduced in the tibialis anterior muscle of the iDicer KO mice, whereas the expression of muscle-enriched miRNAs was only slightly reduced in the Dicer-deficient muscles. After cardiotoxin injection, the iDicer KO mice showed impaired muscle regeneration. We also demonstrated that the number of PAX7+ cells, cell proliferation, and the myogenic differentiation capacity of the primary myoblasts did not differ between the wild-type and the iDicer KO mice. Taken together, these data demonstrate that Dicer is a critical factor for muscle regeneration in vivo.
KW - Dicer
KW - MicroRNA
KW - Muscle regeneration
KW - Skeletal muscle
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U2 - 10.3390/ijms20225686
DO - 10.3390/ijms20225686
M3 - Article
C2 - 31766249
AN - SCOPUS:85075297540
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 22
M1 - 5686
ER -