Acceleration of muscle regeneration by local injection of muscle‐specific microRNAs in rat skeletal muscle injury model

Abstract

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 muscloskeletal 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.

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12skeletal muscle cells

“…miRNAs are short (ϳ20 -25 nucleotides) and noncoding RNA molecules, which repress gene expression by binding to the 3=-untranslated region of target mRNAs and either inhibit translation or promote cleavage of the transcript (1, 13). Recently, muscle-specific miRNAs miR-1, miR-133a, and miR206 have been shown to participate in the regulation of muscle mass (3,17,18,25,29). Some studies have reported that these miRNAs promote proliferation and differentiation of muscle cells (3,18,29), whereas miR-1 and miR-133a seem to be downregulated during skeletal muscle hypertrophy (17,25).…”

“…Recently, muscle-specific miRNAs miR-1, miR-133a, and miR206 have been shown to participate in the regulation of muscle mass (3,17,18,25,29). Some studies have reported that these miRNAs promote proliferation and differentiation of muscle cells (3,18,29), whereas miR-1 and miR-133a seem to be downregulated during skeletal muscle hypertrophy (17,25). Furthermore, upregulations of miR-1 in dexamethasone-mediated muscle atrophy in mice and atrophic signals, which are integrated by miR-1, have been reported (19).…”

The effect of administration of double stranded MicroRNA-210 on acceleration of Achilles tendon healing in a rat model

“…Therefore, several therapeutic trials regulating endogenous miRNA in vivo have been conducted [14][15][16]. miRNA also plays a crucial role in the pathogenesis of disease or trauma in locomotor organs [17][18][19][20][21]. As we known, vascular supply in tendons is very limited and is significantly reduced after injury or rupture.…”

Muscle-specific MicroRNA1 (miR1) Targets Heat Shock Protein 70 (HSP70) during Dexamethasone-mediated Atrophy*

“…Individual microRNAs (miRs) are known to target many mRNAs that control numerous cellular processes (17,18). A cluster of myomiRs including miR1, miR133, and miR206 plays a role in myogenesis and muscle regeneration (19,20). Both miR1 and miR133 were found to be down-regulated in skeletal muscle undergoing hypertrophy and it was proposed that Igf-1 mRNA may be negatively regulated by miR1 in skeletal muscle (21) and cardiac muscle (22).…”