MSTN is a key mediator for low-intensity pulsed ultrasound preventing bone loss in hindlimb-suspended rats

Tang, Liang; An, Shasha; Zhang, Zhihao; Fan, Xiushan; Guo, Jianzhong; Sun, Lijun; Ta, Dean

doi:10.1016/j.bone.2020.115610

Cited by 16 publications

(15 citation statements)

References 51 publications

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“…Marzucanassr et al [52] found an increase in MSTN expression in the muscle of rats with hind limb unloading. In our previous hindlimb unloading model, LIPUS effectively inhibited the expression of MSTN in quadriceps femoris muscle of rats with muscular atrophy [53].Similarly, LIPUS signi cantly inhibited MSTN expression in type 1 diabetic rats, exercise-induced muscle hypertrophy rats and ovariectomized rats [14,17,54].In this study, LIPUS also signi cantly inhibited the expression of MSTN and its receptor at mRNA and protein levels, which may be related to the mechanism of LIPUS improving muscle atrophy.…”

Section: Disscusionsupporting

confidence: 64%

Low-intensity Pulsed Ultrasound Improves Muscle Atrophy in Hindlimb Unloading Rats and its Metabolic Mechanism

Sun¹,

An²,

Zhang³

et al. 2021

Preprint

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Low-intensity pulsed ultrasound (LIPUS) has been proved to promote the proliferation of myoblast C2C12. However, whether LIPUS can effectively prevent muscle atrophy has not been clarified, and if so, what is the possible mechanism. Myostatin (MSTN) is a negtive regulator of skeletal muscle, and inhibition of its expression has a positive effect on the growth and development of skeletal muscle.The aim of this study is to evaluate the effects of LIPUS on muscle atrophyin hind limb unloading rats, and explored the mechanisms. The rats were randomly divided into four groups: normal control group (NC), hind limb unloading group (UL), hind limb unloading plus 30 mW/cm2 irradiation group (UL + 30 mW/cm2), hind limb suspension plus 80 mW/cm2 irradiation group (UL + 80 mW/cm2). The rats were suspended or/and treated with LIPUS for 20 min/d for 28 days. C2C12 cells were exposed to LIPUS at 30 or 80 mW/cm2 for 5 days. After 28 days, LIPUS significantly prevented the decrease of cross-sectional area of muscle fiber and promoted the quality of gastrocnemius muscle. In addition, LIPUS significantly inhibited the content of MSTN in the serum and gastrocnemius muscle of hind limb rats, and its receptor, and promoted myoblast C2C12 proliferation, promoted the stability of alanine, aspartate and glutamate metabolism pathway. These results suggest that the key mechanism of LIPUS in preventing muscle atrophy induced by hind limb unloading may be through inhibiting MSTN and stabilizing alanine, aspartate and glutamate metabolism.

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Section: Disscusionsupporting

confidence: 64%

Low-intensity Pulsed Ultrasound Improves Muscle Atrophy in Hindlimb Unloading Rats and its Metabolic Mechanism

Sun¹,

An²,

Zhang³

et al. 2021

Preprint

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“…To our knowledge, all MSTN knockout animals have developed skeletal muscle development. Continued in-depth study of regulation mechanisms has shown that MSTN regulates the metabolism of the host, including muscle development, fat metabolism [7], glucose metabolism [8,9], bone development [10], and other metabolic processes.…”

Section: Discussionmentioning

confidence: 99%

“…MSTN mutation results in increased muscle mass in many species, including humans [2], sheep [3], mice [4], dogs [5], and cattles [6], without causing severe adverse effects. MSTN not only regulates muscle growth but also plays a vital role in fat metabolism [7], glucose metabolism [8,9], bone development [10], and other metabolic processes [8].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the gut microbiota composition of myostatin mutant cattle prepared using CRISPR/Cas9

2022

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Myostatin (MSTN) negatively regulates muscle development and positively regulates metabolism through various pathways. Although MSTN function in cattle has been widely studied, the changes in the gut microbiota due to MSTN mutation, which contribute to host health by regulating its metabolism, remain unclear. Here, high-throughput sequencing of the 16S rRNA gene was conducted to analyze the gut microbiota of wild-type (WT) and MSTN mutant (MT) cattle. A total of 925 operational taxonomic units (OTUs) were obtained, which were classified into 11 phyla and 168 genera. Alpha diversity results showed no significant differences between MT and WT cattle. Beta diversity analyses suggested that the microbial composition of WT and MT cattle was different. Three dominant phyla and 21 dominant genera were identified. The most abundant bacterial genus had a significant relationship with the host metabolism. Moreover, various bacteria beneficial for health were found in the intestines of MT cattle. Analysis of the correlation between dominant gut bacteria and serum metabolic factors affected by MSTN mutation indicated that MSTN mutation affected the metabolism mainly by three metabolism-related bacteria, Ruminococcaceae_UCG-013, Clostridium_sensu_stricto_1, and Ruminococcaceae_UCG-010. This study provides further insight into MSTN mutation regulating the host metabolism by gut microbes and provides evidence for the safety of gene-edited animals.

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“…Marzucanassr et al [52] found an increase in MSTN expression in the muscle of rats with hindlimb unloading. In our previous hindlimb unloading rat model, LIPUS effectively inhibited the expression of MSTN in quadriceps femoris muscle of rats with muscular atrophy [53]. Similarly, LIPUS significantly inhibited MSTN expression in type 1 diabetic rats, exercise-induced muscle hypertrophy rats and ovariectomized rats [14,17,54].…”

Section: Discussionmentioning

confidence: 76%

Molecular and Metabolic Mechanism of Low-Intensity Pulsed Ultrasound Improving Muscle Atrophy in Hindlimb Unloading Rats

Sun

Zhang

et al. 2021

IJMS

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Low-intensity pulsed ultrasound (LIPUS) has been proved to promote the proliferation of myoblast C2C12. However, whether LIPUS can effectively prevent muscle atrophy has not been clarified, and if so, what is the possible mechanism. The aim of this study is to evaluate the effects of LIPUS on muscle atrophy in hindlimb unloading rats, and explore the mechanisms. The rats were randomly divided into four groups: normal control group (NC), hindlimb unloading group (UL), hindlimb unloading plus 30 mW/cm2 LIPUS irradiation group (UL + 30 mW/cm2), hindlimb unloading plus 80 mW/cm2 LIPUS irradiation group (UL + 80 mW/cm2). The tails of rats in hindlimb unloading group were suspended for 28 days. The rats in the LIPUS treated group were simultaneously irradiated with LIPUS on gastrocnemius muscle in both lower legs at the sound intensity of 30 mW/cm2 or 80 mW/cm2 for 20 min/d for 28 days. C2C12 cells were exposed to LIPUS at 30 or 80 mW/cm2 for 5 days. The results showed that LIPUS significantly promoted the proliferation and differentiation of myoblast C2C12, and prevented the decrease of cross-sectional area of muscle fiber and gastrocnemius mass in hindlimb unloading rats. LIPUS also significantly down regulated the expression of MSTN and its receptors ActRIIB, and up-regulated the expression of Akt and mTOR in gastrocnemius muscle of hindlimb unloading rats. In addition, three metabolic pathways (phenylalanine, tyrosine and tryptophan biosynthesis; alanine, aspartate and glutamate metabolism; glycine, serine and threonine metabolism) were selected as important metabolic pathways for hindlimb unloading effect. However, LIPUS promoted the stability of alanine, aspartate and glutamate metabolism pathway. These results suggest that the key mechanism of LIPUS in preventing muscle atrophy induced by hindlimb unloading may be related to promoting protein synthesis through MSTN/Akt/mTOR signaling pathway and stabilizing alanine, aspartate and glutamate metabolism.

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MSTN is a key mediator for low-intensity pulsed ultrasound preventing bone loss in hindlimb-suspended rats

Cited by 16 publications

References 51 publications

Low-intensity Pulsed Ultrasound Improves Muscle Atrophy in Hindlimb Unloading Rats and its Metabolic Mechanism

Low-intensity Pulsed Ultrasound Improves Muscle Atrophy in Hindlimb Unloading Rats and its Metabolic Mechanism

Analysis of the gut microbiota composition of myostatin mutant cattle prepared using CRISPR/Cas9

Molecular and Metabolic Mechanism of Low-Intensity Pulsed Ultrasound Improving Muscle Atrophy in Hindlimb Unloading Rats

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