Influence of myostatin on skeletal muscle plasticity (1102.22)

Abstract

Goal: to investigate the role of myostatin (Mst) in adult skeletal muscle structure, function and physical performance. We generated the conditional Mst overexpressing transgenic (CMOT) mice in which Mst expression can be switched ON or OFF. Methods: We used mechanical overloading (MO) (bilateral synergist ablation of plantaris muscle) to determine the role of Mst in muscle structure and function in Mst KO (knockout), TG (transgenic), CMOT and WT (wild type) animals. Results: In CMOT mice, Mst level was 5 ‐10 times higher compared to WT followed by doxycyclin treatment. After 6 weeks of MO surgery, plantaris muscle specific tension was the highest, but not significant in CMOT; muscle mass increased in each groups, the biggest increase (200%) was in Mst TG; total cross sectional area and fiber number had increased with the highest rate (2.3x and 1,4x, respectively) in CMOT. Succinate dehydrogenase (SDH) was determined, SDH positive fiber number significantly increased in Mst KO and CMOT; the oxidative fiber ratio was the highest (45.3%), while the SHD negative fiber ration was the lowest (21.6%) in CMOT mice. In CMOT animals, TGF‐beta, insulin, Wnt, LDL, PI3K/Akt and p53 signaling pathways were up‐regulated. Conclusion: We have established an animal model, the CMOT with which we can investigate the correlation between Mst levels and muscle wasting in adulthood and the possible therapeutic intervention of muscle loss.Grant Funding Source: NIH/NIAMSD R21AR054101