The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

Winbanks, Catherine E.; Qian, Hongwei; Liu, Yingying; Bernardo, Bianca C.; Beyer, Claudia; Watt, Kevin I.; Thomson, Russell; Connor, Timothy; Turner, Bradley J.; McMullen, Julie R.; Larsson, Lars; McGee, Sean L.; Harrison, Craig A.; Gregorevic, Paul

doi:10.1083/jcb.201211134

Cited by 183 publications

(203 citation statements)

References 61 publications

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“…HGF is a regulator of satellite cells (44) and transmits signals through Smad2/3. The BMP-mediated Smad1/5/8 signaling is an important regulator of skeletal muscle mass (37,52), hepatocyte proliferation, and liver regeneration and function (11,41). Comparing the genotypes, phospho-Smad1/5/8 levels show the same pattern as tissue weight/body weight ratios in both skeletal muscle and liver, suggesting the impact of Smad1/5/8 signaling on regulation of skeletal muscle and liver size.…”

Section: Discussionmentioning

confidence: 82%

Myostatin propeptide mutation of the hypermuscularCompactmice decreases the formation of myostatin and improves insulin sensitivity

Kocsis

Trencsényi²,

Szabó

et al. 2017

American Journal of Physiology-Endocrinology and Metabolism

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The TGF␤ family member myostatin (growth/differentiation factor-8) is a negative regulator of skeletal muscle growth. The hypermuscular Compact mice carry the 12-bp Mstn(Cmpt-dl1Abc) deletion in the sequence encoding the propeptide region of the precursor promyostatin, and additional modifier genes of the Compact genetic background contribute to determine the full expression of the phenotype. In this study, by using mice strains carrying mutant or wild-type myostatin alleles with the Compact genetic background and nonmutant myostatin with the wild-type background, we studied separately the effect of the Mstn(Cmpt-dl1Abc) mutation or the Compact genetic background on morphology, metabolism, and signaling. We show that both the Compact myostatin mutation and Compact genetic background account for determination of skeletal muscle size. Despite the increased musculature of Compacts, the absolute size of heart and kidney is not influenced by myostatin mutation; however, the Compact genetic background increases them. Both Compact myostatin and genetic background exhibit systemic metabolic effects. The Compact mutation decreases adiposity and improves whole body glucose uptake, insulin sensitivity, and 18 FDG uptake of skeletal muscle and white adipose tissue, whereas the Compact genetic background has the opposite effect. Importantly, the mutation does not prevent the formation of mature myostatin; however, a decrease in myostatin level was observed, leading to altered activation of Smad2, Smad1/ 5/8, and Akt, and an increased level of p-AS160, a Rab-GTPaseactivating protein responsible for GLUT4 translocation. Based on our analysis, the Compact genetic background strengthens the effect of myostatin mutation on muscle mass, but those can compensate for each other when systemic metabolic effects are compared.

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Section: Discussionmentioning

confidence: 82%

Myostatin propeptide mutation of the hypermuscularCompactmice decreases the formation of myostatin and improves insulin sensitivity

Kocsis

Trencsényi²,

Szabó

et al. 2017

American Journal of Physiology-Endocrinology and Metabolism

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“…It becomes activated in the absence of the prohypertrophic, transforming growth factor-␤ family member bone morphogenetic protein (BMP) (FIGURE 6C; Refs. 384,457).…”

Section: Protein Degradationmentioning

confidence: 97%

Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting

Tintignac

Brenner

Rüegg

2015

Physiological Reviews

332

341

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The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this conversion and result in loss of ambulation and respiration. The loss of motor input also causes muscle wasting as muscle mass is constantly adapted to contractile needs by the balancing of protein synthesis and protein degradation. Finally, neuromuscular activity and muscle mass have a major impact on metabolic properties of the organisms. This review discusses the mechanisms involved in the development and maintenance of the neuromuscular junction, the consequences of and the mechanisms involved in its dysfunction, and its role in maintaining muscle mass during aging. As life expectancy is increasing, loss of muscle mass during aging, called sarcopenia, has emerged as a field of high medical need. Interestingly, aging is also accompanied by structural changes at the neuromuscular junction, suggesting that the mechanisms involved in neuromuscular junction maintenance might be disturbed during aging. In addition, there is now evidence that behavioral paradigms and signaling pathways that are involved in longevity also affect neuromuscular junction stability and sarcopenia.

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Section: Discussionmentioning

confidence: 85%

“…Beside the increased serum myostatin levels an increase of the intramuscular myostatin level was detected in HIV-infected patients [49] and patients with cancer cachexia [51]. Furthermore, the myostatin mRNA levels were elevated in chronic disuse wasted muscle [52].…”

Section: Myostatin and Diseasesmentioning

confidence: 99%

Glycogen distribution and metabolic alterations in the hypermuscular, myostatin mutant compact mice

Kocsis¹

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The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

Abstract: The BMP signaling pathway promotes muscle growth and inhibits muscle wasting via SMAD1/5-dependent signaling.

Cited by 183 publications

References 61 publications

Myostatin propeptide mutation of the hypermuscularCompactmice decreases the formation of myostatin and improves insulin sensitivity

Myostatin propeptide mutation of the hypermuscularCompactmice decreases the formation of myostatin and improves insulin sensitivity

Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting

Glycogen distribution and metabolic alterations in the hypermuscular, myostatin mutant compact mice

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