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Inhibition of MSTN signal pathway may participate in LIPUS preventing bone loss in ovariectomized rats

Journal of Bone and Mineral Metabolism volume 38, pages 14–26 (2020)Cite this article

Abstract

Introduction

Menopause can lead to osteoporosis, which is characterized by destruction of bone microstructure, poor mechanical properties, and prone to fracture. LIPUS can effectively promote bone formation and fracture healing. MSTN is a transforming growth factor-β family member that acts as a negative regulator of skeletal muscle growth. A MSTN deficiency also has a positive effect on bone formation. However, whether LIPUS could inhibit bone loss and promote healing of bone injury of menopause through the inhibition of the MSTN signaling pathway has not been previously investigated. We herein investigated the effects of LIPUS on bone architecture, mechanical properties, the healing of bone defects, and its potential molecular mechanisms in ovariectomized rats.

Materials and methods

The rats were randomly divided into three groups: sham ovariectomized group (Sham), ovariectomized model group (OVX), ovariectomized model with LIPUS therapy group (OVX + LIPUS). The OVX + LIPUS rats were treated with LIPUS (1.5 MHz, 30 mW/cm2) on the femur for 20 min/day that lasted for 19 days.

Results

LIPUS effectively improved the bone microstructure, increased mechanical properties and promoted the healing of bone defects in ovariectomized rats. Moreover, LIPUS effectively decreased the MSTN content in serum and quadriceps muscle in ovariectomized rats, and inhibited the expression of MSTN downstream signaling molecules and activated the Wnt signaling pathway in the femur.

Conclusions

The present study shows that LIPUS improved osteoporosis and promoted bone defect healing in the ovariectomized rats may through the inhibition of the MSTN signal pathway.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (nos. 11827808, 11774213, 11727813, 11502134 and 11525416), the Natural Science Foundation of Shaanxi Province (2018JM1022), the Fundamental Research Funds for the Central Universities (GK201703092 and GK201703091) and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01).

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Author notes

  1. Liang Tang and Yiting Kang contributed equally to this work and should be regarded as co-first authors.

Affiliations

  1. Institute of Sports Biology, Shaanxi Normal University, Xi’an, 710119, China

    Liang Tang, Yiting Kang, Tingting Zhao, Wenxin Cao, Xiushan Fan & Lijun Sun

  2. Department of Electronic Engineering, Fudan University, Shanghai, 200433, China

    Shuxin Sun & Dean Ta

  3. Shaanxi Key Laboratory of Ultrasonics, Shaanxi Normal University, Xi’an, 710119, China

    Jianzhong Guo

  4. Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, China

    Yiting Kang

  5. Human Phenome Institute, Fudan University, Shanghai, 201203, China

    Dean Ta

  6. Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention (MICCAI) of Shanghai, Shanghai, 200032, China

    Dean Ta

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  1. Liang Tang
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Contributions

All authors participated in the design, interpretation of the studies, analysis of the data and review of the manuscript. LT, LS and DT designed the experiments. YK conducted the experiments and performed analysis. SX, TZ, WC and XF participated in the establishment of the animal model and LIPUS treatment. DT and JG designed the LIPUS instrument. YK and LS wrote the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lijun Sun or Dean Ta.

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Conflicts of interest

Liang Tang, Yiting Kang, Shuxin Sun, Tingting Zhao, Wenxin Cao, Xiushan Fan, Jianzhong Guo, Lijun Sun and Dean Ta declare that they have no conflict of interest.

Ethical approval

All procedures were approved by the Animal Ethical Committee of Shaanxi Normal University, and carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978).

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Tang, L., Kang, Y., Sun, S. et al. Inhibition of MSTN signal pathway may participate in LIPUS preventing bone loss in ovariectomized rats. J Bone Miner Metab 38, 14–26 (2020). https://doi.org/10.1007/s00774-019-01029-5

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  • DOI: https://doi.org/10.1007/s00774-019-01029-5

Keywords

  • Osteoporosis
  • Low-intensity pulsed ultrasound
  • Bone defect healing
  • Bone microstructure
  • Myostatin