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

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

10.21203/rs.3.rs-389558/v1 ◽

2021 ◽

Author(s):

Lijun Sun ◽

Shasha An ◽

Zhihao Zhang ◽

Yaling Zhou ◽

Zhanke Ma ◽

...

Keyword(s):

Muscle Atrophy ◽

Hind Limb ◽

Gastrocnemius Muscle ◽

C2c12 Cells ◽

Glutamate Metabolism ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Irradiation Group ◽

Hind Limb Unloading

Abstract 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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Low intensity pulsed ultrasound information technology intervention in diagnosis and prediction of Muscle Atrophy

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.37.6-wit.4839 ◽

2021 ◽

Vol 37 (6-WIT) ◽

Author(s):

Zhijun Sun

Keyword(s):

Information Technology ◽

Body Weight ◽

Muscle Atrophy ◽

Gastrocnemius Muscle ◽

Weight Bearing ◽

Good Effect ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Technology Intervention

Objective: To discuss the effects and function of LIPUS on muscle atrophy (MA), analysis from various aspects through the study of low-intensity pulsed ultrasound (LIPUS) information technology intervention (ITI) in diagnosis and the prediction of muscle atrophy.. Method: In this study conducted in our university, 74 healthy female SD rats aged three months, weighing 100-200g were selected. All rats were placed in sterile cages from June 2020 to September 2020. They were divided into three groups. In the OVO group and OVE group, the mice are treated with LIPUS, Finally, the changes of body weight, grasping power, biochemical indexes and glycogen content of gastrocnemius muscle were analyzed and recorded to explore the effect and value of LIPUS ITI combined with intermittent weight-bearing exercise in the treatment of MA Results: After weight-bearing running, the body weight of model (OVO) group, exercise (OVE) group and NC group had significant statistical significance (P<0.01). It was found that the weight of OVE group was much more as compared to OVO group. There was significant difference in body weight between OVO group and NC group (P<0.05). After LIPUS treatment, it was found that the weight of OVO group, OVE group, LIPUS group and OVE +LIPUS group increased. Compared with the NC group, there was significant statistical difference (P<0.01). Conclusion: Low intensity pulsed ultrasound ITI has a good effect on improving MA, so as to effectively improve the weight of gastrocnemius muscle. The combined application of the two is better for the improvement of muscular atrophy. doi: https://doi.org/10.12669/pjms.37.6-WIT.4839 How to cite this:Sun Z. Low intensity pulsed ultrasound information technology intervention in diagnosis and prediction of Muscle Atrophy. Pak J Med Sci. 2021;37(6):1569-1573. doi: https://doi.org/10.12669/pjms.37.6-WIT.4839 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Effects of low-intensity pulsed ultrasound on the differentiation of C2C12 cells

Life Sciences ◽

10.1016/j.lfs.2006.06.029 ◽

2006 ◽

Vol 79 (20) ◽

pp. 1936-1943 ◽

Cited By ~ 72

Author(s):

Kyoko Ikeda ◽

Tadahiro Takayama ◽

Naoto Suzuki ◽

Koichi Shimada ◽

Kichibee Otsuka ◽

...

Keyword(s):

C2c12 Cells ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity

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Low-intensity pulsed ultrasound prevents muscle atrophy induced by type 1 diabetes in rats

Skeletal Muscle ◽

10.1186/s13395-017-0145-7 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 9

Author(s):

Liang Tang ◽

Nan Li ◽

Wenqi Jian ◽

Yiting Kang ◽

Bo Yin ◽

...

Keyword(s):

Type 1 Diabetes ◽

Muscle Atrophy ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity

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Faculty Opinions recommendation of Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726483280.793536472 ◽

2017 ◽

Author(s):

Jaspreet Sandhu

Keyword(s):

Pelvic Pain ◽

Chronic Prostatitis ◽

Chronic Pelvic Pain ◽

Chronic Pelvic Pain Syndrome ◽

Pain Syndrome ◽

Pelvic Pain Syndrome ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity

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Improved activity of MC3T3-E1 cells by the exciting piezoelectric BaTiO3/TC4 using low-intensity pulsed ultrasound

Bioactive Materials ◽

10.1016/j.bioactmat.2021.04.016 ◽

2021 ◽

Vol 6 (11) ◽

pp. 4073-4082

Author(s):

Kunzhan Cai ◽

Yilai Jiao ◽

Quan Quan ◽

Yulin Hao ◽

Jie Liu ◽

...

Keyword(s):

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity

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Development and Validation of Low-Intensity Pulsed Ultrasound Systems for Highly Controlled in vitro Cell Stimulation

Ultrasonics ◽

10.1016/j.ultras.2021.106495 ◽

2021 ◽

pp. 106495

Author(s):

F. Fontana ◽

F. Iberite ◽

A. Cafarelli ◽

A. Aliperta ◽

G. Baldi ◽

...

Keyword(s):

Pulsed Ultrasound ◽

Cell Stimulation ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Development And Validation

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Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing

Scientific Reports ◽

10.1038/s41598-021-89672-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tatsuya Shimizu ◽

Naomasa Fujita ◽

Kiyomi Tsuji-Tamura ◽

Yoshimasa Kitagawa ◽

Toshiaki Fujisawa ◽

...

Keyword(s):

Fracture Healing ◽

Transcriptional Control ◽

Target Genes ◽

Pulsed Ultrasound ◽

Activated T Cells ◽

In Vivo Models ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Ultrasound Stimulation

AbstractUltrasound stimulation is a type of mechanical stress, and low-intensity pulsed ultrasound (LIPUS) devices have been used clinically to promote fracture healing. However, it remains unclear which skeletal cells, in particular osteocytes or osteoblasts, primarily respond to LIPUS stimulation and how they contribute to fracture healing. To examine this, we utilized medaka, whose bone lacks osteocytes, and zebrafish, whose bone has osteocytes, as in vivo models. Fracture healing was accelerated by ultrasound stimulation in zebrafish, but not in medaka. To examine the molecular events induced by LIPUS stimulation in osteocytes, we performed RNA sequencing of a murine osteocytic cell line exposed to LIPUS. 179 genes reacted to LIPUS stimulation, and functional cluster analysis identified among them several molecular signatures related to immunity, secretion, and transcription. Notably, most of the isolated transcription-related genes were also modulated by LIPUS in vivo in zebrafish. However, expression levels of early growth response protein 1 and 2 (Egr1, 2), JunB, forkhead box Q1 (FoxQ1), and nuclear factor of activated T cells c1 (NFATc1) were not altered by LIPUS in medaka, suggesting that these genes are key transcriptional regulators of LIPUS-dependent fracture healing via osteocytes. We therefore show that bone-embedded osteocytes are necessary for LIPUS-induced promotion of fracture healing via transcriptional control of target genes, which presumably activates neighboring cells involved in fracture healing processes.

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