MiR‐682 Antisense Inhibits Skeletal Muscle Regeneration

Skeletal muscle regeneration is mediated by myogenic progenitor cell (MPC) proliferation and differentiation. We have previously documented that the microRNA (miRNA), miR‐682, is the only miRNA significantly up‐regulated in proliferating MPC in vitro and knocking down miR‐682 expression significantly inhibited MPC proliferation. The present study examined the biological function of miR‐682 on muscle regeneration in C57/BL6 male mice. Using quantitative PCR array, miR‐682 was maximally expressed within 24 hours after cardiotoxin (CTX)‐induced tibialis anterior (TA) muscle injury. Locked‐nucleic‐acid‐modified oligonucleotides, LNA‐anti‐miR‐682, were administered intraperitoneally 1 day prior to CTX injection. Increasing doses of LNA‐anti‐miR‐682 resulted in decreasing expression of miR‐682 in TA muscle at day 1 post‐CTX. Muscle regeneration was evaluated at day 4 post‐CTX after pretreatment with either LNA‐anti‐miR‐682 or scramble oligonucleotide (10 mg/kg). Small, regenerated muscle fibers with centrally‐located nuclei were widespread in animals treated with scramble oligonucleotide. In striking contrast, regenerated muscle fibers were scant and necrotic myofibers predominated in animals treated with anti‐miR‐682. Thus, miR‐682 appears to be integral to muscle regeneration in vivo. Supported by the Veterans Administration, AR059096, HL07446 and HL074236.