Key result
Tenotomy induces faster atrophy and distinct degradation pathways than casting despite equivalent 14-day muscle loss.
Why the study?
Multiple mechanisms leading to skeletal muscle atrophy exist, but the distinct molecular pathways in different disuse models are not fully understood.
Do different disuse models of skeletal muscle atrophy induce distinct protein degradation profiles?
Do different disuse models of skeletal muscle atrophy induce distinct protein degradation profiles?
Different models of skeletal muscle atrophy induce distinct protein degradation pathways, suggesting that specific therapeutic agents may be necessary for different atrophic conditions.
Different disuse models activate distinct proteolytic pathways in rodent muscle; leaves open etiology-specific therapies pending human validation.
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.
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Bialek et al. (2011) studied Skeletal muscle atrophy. Achilles tendon laceration (tenotomy) vs. Hindlimb casting was evaluated on Muscle loss (wet weight and muscle fiber size) and molecular changes. Achilles tendon laceration and hindlimb casting resulted in equivalent muscle loss at 14 days, but tenotomy induced more rapid atrophy and distinct degradation pathways.
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