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MSTN is an important myokine for weight-bearing training to attenuate bone loss in ovariectomized rats

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Abstract

Weight-bearing training, as one of resistance exercises, is beneficial to bone health. Myostatin (MSTN) is a negative regulator of skeletal muscle growth and development. Animals lacking MSTN show increased bone mineral density (BMD). The aim of this study was to investigate the preventive effect of weight-bearing training on bone loss in ovariectomized rats and whether it was related to MSTN. In this study, the rats were randomly assigned to three group: Sham-ovariectomized (Sham), ovariectomized (OVX), ovariectomized and weight-bearing training (OWT). The rats in the OWT group ran at 20-m/min bearing with 35% of their body weight for 6 days/week. After 10 weeks, compared with the OVX group, weight-bearing training increased the BMD of total femur and trabecular bone by 8.13% and 57.44%, respectively. The OVX-induced destruction of bone microarchitecture including the thickness and number of trabeculae and bone volume fraction was all significantly improved (9.26%, 47.68%, 63.03%) in the OWT group. The OVX-induced degradation of bone mechanical properties was significantly enhanced in the OWT group (maximum load increased by 35.46%, stiffness increased by 89.19%, energy absorption increased by 53.4%; elastic modulus increased by 26.3%). Ten-week weight-bearing training also significantly upregulated the mRNA and protein expression of Wnt1 and β-catenin, which is crucial in bone development. Compared with the Sham group, MSTN in serum and muscle increased in the OVX group, but it decreased in the OWT group compared with the OVX group. Its receptor ActRIIB and downstream molecules Smad2/3 in the OVX group were downregulated in bone by weight-bearing training. The results indicated that MSTN is an important myokine for weight-bearing training to attenuate bone loss in ovariectomized rats.

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Funding

This work was supported by the National Natural Science Foundation of China (Nos. 11974233, 11774213, and 11502134), the Natural Science Foundation of Shaanxi Province (2018JM1022), and the Fundamental Research Funds for the Central Universities (GK202103123).

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

Authors and Affiliations

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

    Liang Tang, Tingting Zhao, Yiting Kang, Shasha An, Xiushan Fan & Lijun Sun

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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 and LS designed the experiments. TZ conducted the experiments and performed the analysis. YK, SA, and XF participated in the establishment of the animal model and exercise training. TZ and LS wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Lijun Sun.

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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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The authors declare no competing interests.

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Key points

1. Weight-bearing training partially prevented bone loss in ovariectomized rats.

2. Weight-bearing training suppressed MSTN expression in muscle and serum.

3. Weight-bearing training inhibited the downstream molecules of MSTN in the bone.

4. Wnt/β-catenin bone formation pathway was also activated.

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Tang, L., Zhao, T., Kang, Y. et al. MSTN is an important myokine for weight-bearing training to attenuate bone loss in ovariectomized rats. J Physiol Biochem 78, 61–72 (2022). https://doi.org/10.1007/s13105-021-00838-5

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