Contractile properties of EDL and soleus muscles of myostatin-deficient mice

Abstract

Myostatin is a negative regulator of muscle mass. The impact of myostatin deficiency on the contractile properties of healthy muscles has not been determined. We hypothesized that myostatin deficiency would increase the maximum tetanic force (P(o)), but decrease the specific P(o) (sP(o)) of muscles and increase the susceptibility to contraction-induced injury. The in vitro contractile properties of extensor digitorum longus (EDL) and soleus muscles from wild-type (MSTN(+/+)), heterozygous-null (MSTN(+/-)), and homozygous-null (MSTN(-/-)) adult male mice were determined. For EDL muscles, the P(o) of both MSTN(+/-) and MSTN(-/-) mice were greater than the P(o) of MSTN(+/+) mice. For soleus muscles, the P(o) of MSTN(-/-) mice was greater than that of MSTN(+/+) mice. The sP(o) of EDL muscles of MSTN(-/-) mice was less than that of MSTN(+/+) mice. For soleus muscles, however, no difference in sP(o) was observed. Following two lengthening contractions, EDL muscles from MSTN(-/-) mice had a greater force deficit than that of MSTN(+/+) or MSTN(+/-) mice, whereas no differences were observed for the force deficits of soleus muscles. Myostatin-deficient EDL muscles had less hydroxyproline, and myostatin directly increased type I collagen mRNA expression and protein content. The difference in the response of EDL and soleus muscles to myostatin may arise from differences in the levels of a myostatin receptor, activin type IIB. Compared with the soleus, the amount of activin type IIB receptor was approximately twofold greater in EDL muscles. The results support a significant role for myostatin not only in the mass of muscles but also in the contractility and the composition of the extracellular matrix of muscles.

Myostatin deficiency is associated with lipidomic abnormalities in skeletal muscles

“…Here, we showed that Mstn gene deletion results in reduced lipolytic machinery in Mstn deficient hypertrophic muscles (impaired mitochondrial yield, CS and β-HAD activities and Cpt1 and Ppar- gene expressions), in line with previous studies showing that oxidative metabolism is diminished in several models of Mstn deficiency [12,13,15,16,51]. In addition, we demonstrated that the levels of cytosolic (FABP3) and sarcolemmal lipid transporters (FATP1, FATP4) are reduced, in agreement with our previous observation showing a significant reduction of FAT/CD36 levels [16].…”

“…Indeed, beyond muscle hypertrophy, Mstn KO mice show a disturbed muscle function with loss of muscle strength and endurance in vivo or ex vivo accompanied with a decrease in mechanical performance, and ATP production during exercise [11,12,13,14]. In parallel, many other metabolic changes have been documented in Mstn KO muscle such as a decrease in mitochondrial content, disturbance in mitochondrial respiratory function with a decay in the respiratory control ratio in intermyofibrillar mitochondria, and a decline in porine activity [11,13,15].…”

Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle

“…Muscle mass, fiber length, and maximum isometric tetanic force were measured. These measurements were used to determine total crosssectional area and specific force (kN/m 2 ) (53,57). The susceptibility to contraction-induced injury was determined after lengthening contractions.…”

Deletion of Mbtps1 (Pcsk8, S1p, Ski-1) Gene in Osteocytes Stimulates Soleus Muscle Regeneration and Increased Size and Contractile Force with Age

“…For example, myostatin-null mice gain mass in both their EDL and SOL; however, functional testing shows that specific contractile force is less than controls for myostatin cKO EDL and the same as controls for cKO SOL (55)(56)(57). Conditional deletion of IGF-1 in muscle was found to be selective for fast twitch EDL where mass and maximum power increased about 30% (58).…”