Acceleration of muscle regeneration by local injection of muscle-specific microRNAs in rat skeletal muscle injury model.
MicroRNA (miRNA)s are a class of non-coding RNAs that regulate gene expression post-transcriptionally. Muscle-specific miRNA, miRNA (miR)-1, miR-133 and miR-206 play a crucial role in the regulation of muscle development and homeostasis. Muscle injuries are a common musculoskeletal disorder, and the most effective treatment has not been established yet. The purpose of this study was to demonstrate that a local injection of double-stranded (ds) miR-1, miR-133 and 206 can accelerate muscle regeneration in a rat skeletal muscle injury model. After the laceration of the rat tibialis anterior muscle, ds miR-1, 133 and 206 mixture mediated atelocollagen was injected into the injured site. The control group was injected with control siRNA. At 1 week after injury, an injection of miRNAs could enhance muscle regeneration morphologically and physiologically, and prevent fibrosis effectively compared to the control siRNA. Administration of exogenous miR-1, 133 and 206 can induce expression of myogenic markers, MyoD1, myogenin and Pax7 in mRNA and expression in the protein level at 3 and 7 days after injury. The combination of miR-1, 133 and 206 can promote myotube differentiation, and the expression of MyoD1, myogenin and Pax7 were up-regulated in C2C12 cells in vitro. Local injection of miR-1, 133 and 206 could be a novel therapeutic strategy in the treatment of skeletal muscle injury.
Nakasa
Tomoyuki
T
Department of Orthopaedic Surgery, Programs for Applied Biomedicine, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima, Japan. tnakasa@smn.enjoy.ne.jp
Ishikawa
Masakazu
M
Shi
Ming
M
Shibuya
Hayatoshi
H
Adachi
Nobuo
N
Ochi
Mitsuo
M
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000378:metabolism*; D023421:Models, Animal; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000293:injuries*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D055435:Myostatin / Q000235:genetics / Q000378:metabolism; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D012038:Regeneration; D015854:Up-Regulation
D035683:MicroRNAs; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018008:Myogenin; D055435:Myostatin; C530821:PAX7 protein, rat; D051761:Paired Box Transcription Factors