Extracellular microRNAs (miRNAs) are promising biomarkers of the inherited 
muscle wasting condition Duchenne muscular dystrophy, as they allow non-invasive 
monitoring of either disease progression or response to therapy. In this study, 
serum miRNA profiling reveals a distinct extracellular miRNA signature in 
dystrophin-deficient mdx mice, which shows profound dose-responsive restoration 
following dystrophin rescue. Extracellular dystrophy-associated miRNAs 
(dystromiRs) show dynamic patterns of expression that mirror the progression of 
muscle pathology in mdx mice. Expression of the myogenic miRNA, miR-206 and the 
myogenic transcription factor myogenin in the tibialis anterior muscle were 
found to positively correlate with serum dystromiR levels, suggesting that 
extracellular miRNAs are indicators of the regenerative status of the 
musculature. Similarly, extracellular dystromiRs were elevated following 
experimentally-induced skeletal muscle injury and regeneration in non-dystrophic 
mice. Only a minority of serum dystromiRs were found in extracellular vesicles, 
whereas the majority were protected from serum nucleases by association with 
protein/lipoprotein complexes. In conclusion, extracellular miRNAs are dynamic 
indices of pathophysiological processes in skeletal muscle.