title: Combination of small RNAs for skeletal muscle regeneration.
abstract: Selectively controlling the expression of the target genes through RNA interference (RNAi) has significant therapeutic potential for injuries or diseases of tissues. We used this strategy to accelerate and enhance skeletal muscle regeneration for the treatment of muscular atrophy. In this study, we used myostatin small interfering (si)RNA (siGDF-8), a major inhibitory factor in the development and postnatal regeneration of skeletal muscle and muscle-specific microRNAs (miR-1 and -206) to further accelerate muscle regeneration. This combination of 3 small RNAs significantly improved the gene expression of myogenic regulatory factors in vitro, suggesting myogenic activation. Moreover, cell proliferation and myotube formation improved without compromising each other, which indicates the myogenic potential of this combination of small RNAs. The recovery of chemically injured tibialis anterior muscles in rats was significantly accelerated, both functionally and structurally. This novel combination of siRNA and miRNAs has promising therapeutic potential to improve in situ skeletal muscle regeneration.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: NaJung
authors.initials: N
authors.lastname: Kim
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Yoo
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA sjlee@wakehealth.edu.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D015870:Gene Expression; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D024510:Muscle Development / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D009133:Muscular Atrophy / Q000235:genetics / Q000503:physiopathology; D032446:Myoblasts / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000235:genetics; D055435:Myostatin / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D018006:Myogenic Regulatory Factors; D055435:Myostatin; D034741:RNA, Small Interfering; D012313:RNA
keywords: RNAi; miR; regeneration; siRNA; tissue engineering