Skeletal muscle
atrophy can be a consequence of many diseases, environmental insults, inactivity, age, and injury.
Atrophy is characterized by active degradation, removal of
contractile proteins, and a reduction in muscle fiber size. Animal models have been extensively used to identify pathways that lead to atrophic conditions. We used genome-wide expression profiling analyses and quantitative PCR to identify the molecular changes that occur in two clinically relevant mouse models of
muscle atrophy: hindlimb casting and Achilles tendon
laceration (
tenotomy). Gastrocnemius muscle samples were collected 2, 7, and 14 days after casting or injury. The total amount of muscle loss, as measured by wet weight and muscle fiber size, was equivalent between models on day 14, although
tenotomy resulted in a more rapid induction of
muscle atrophy. Furthermore,
tenotomy resulted in the regulation of significantly more
mRNA transcripts then did casting. Analysis of the regulated genes and pathways suggest that the mechanisms of
atrophy are distinct between these models. The degradation following casting was
ubiquitin-
proteasome mediated, while degradation following
tenotomy was lysosomal and
matrix-metalloproteinase mediated, suggesting a possible role for autophagy. These data suggest that there are multiple mechanisms leading to
muscle atrophy and that specific therapeutic agents may be necessary to combat
atrophy resulting from different conditions.