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

  • Liang Tang
  • Yiting Kang
  • Shuxin Sun
  • Tingting Zhao
  • Wenxin Cao
  • Xiushan Fan
  • Jianzhong Guo
  • Lijun SunEmail author
  • Dean TaEmail author
Original Article



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.


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.


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.


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



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).

Author 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.

Compliance with ethical standards

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).

Supplementary material

774_2019_1029_MOESM1_ESM.doc (8 mb)
Supplementary material 1 (DOC 8243 kb)


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Copyright information

© The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Liang Tang
    • 1
  • Yiting Kang
    • 1
    • 4
  • Shuxin Sun
    • 2
  • Tingting Zhao
    • 1
  • Wenxin Cao
    • 1
  • Xiushan Fan
    • 1
  • Jianzhong Guo
    • 3
  • Lijun Sun
    • 1
    Email author
  • Dean Ta
    • 2
    • 5
    • 6
    Email author
  1. 1.Institute of Sports BiologyShaanxi Normal UniversityXi’anChina
  2. 2.Department of Electronic EngineeringFudan UniversityShanghaiChina
  3. 3.Shaanxi Key Laboratory of UltrasonicsShaanxi Normal UniversityXi’anChina
  4. 4.Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and TechnologyXi’an Jiaotong UniversityXi’anChina
  5. 5.Human Phenome InstituteFudan UniversityShanghaiChina
  6. 6.Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention (MICCAI) of ShanghaiShanghaiChina

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