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Effects of Whole-Body Vibration on Breast Cancer Bone Metastasis and Vascularization in Mice

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Abstract

We evaluated whether whole-body vibration (WBV) prevented bone loss induced by breast cancer (BC) metastasis and the involvement of bone marrow vasculature. One day after orthotopic transplantation of mammary 4T1 tumor cells, 8-week-old BALB/c mice were subjected to 0.3 g/90 Hz vertical vibration for 20 min/day for 5 days/week (BC-WBV) or sham-handled (BC-Sham) over 3 weeks. Age-matched intact mice (Intact) were also sham-handled. Both tibiae were harvested from BC-WBV (n = 7), BC-Sham (n = 9), and Intact (n = 5) mice for bone structure imaging by synchrotron radiation-based computed tomography (SRCT) and hematoxylin and eosin staining, whereas right tibiae were harvested from other BC-WBV and BC-Sham (n = 6 each) mice for vascular imaging by SRCT. Tumor cells were similarly widespread in the marrow in BC-WBV and BC-Sham mice. In BC-Sham mice, cortical bone volume, trabecular volume fraction, trabecular thickness, trabecular number density, and bone mineral density were smaller, and marrow volume and trabecular separation were larger than in Intact mice. However, although trabecular thickness was smaller in BC-WBV than Intact mice, the others did not differ between the two groups. Serum osteocalcin tended to be higher in BC-WBV than BC-Sham mice. Compared with BC-Sham mice, BC-WBV mice had a smaller vessel diameter, a trend of a larger vessel number density, and smaller vessel diameter heterogeneity. In conclusion, WBV mitigates bone loss in BC bone metastasis, which may be partly due to increased bone anabolism. The alteration of marrow vasculature appears to be favorable for anti-tumor drug delivery. Further studies are needed to clarify the multiple actions of WBV on bone, tumor, and marrow vasculature and how they contribute to bone protection in BC metastasis.

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Acknowledgements

The authors are indebted to Shinya Itamochi (Osaka University Graduate School of Engineering Science) for his assistance with animal experiments and SRCT imaging and to Dr. Takashi Fukushima (Saitama Medical University International Medical Center) for his help in the interpretation of the histological data. We would also like to thank Mitchell Arico from Edanz (https://jp.edanz.com/ac) for editing the draft of this manuscript.

Funding

A part of this study was supported by Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (Grant Nos. 26282120, 15K12509, and 20K21899).

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Authors and Affiliations

  1. Biomedical Engineering Laboratory, Tokushima University Graduate School of Technology, Industrial and Social Sciences, 770-8506, Tokushima, Japan

    Takeshi Matsumoto

  2. Biomedical Engineering Laboratory, Tokushima University Faculty of Science and Technology, 770-8506, Tokushima, Japan

    Akihiro Mukohara

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  1. Takeshi Matsumoto
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Correspondence to Takeshi Matsumoto.

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Takeshi Matsumoto and Akihiro Mukohara declare that they have no conflict of interest.

Ethical Approval

All animal experiments were approved by the Ethics Committee on Animal Experiments of Tokushima University.

Human and Animal Rights and Informed Consent statement

All animals involved in the study were cared for in accordance with the Declaration of Helsinki. The protocol of animal treatment was in accordance with the guiding principles of the Care and Use of Laboratory Animals of Tokushima University. No human studies were performed in the course of the experiments.

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Matsumoto, T., Mukohara, A. Effects of Whole-Body Vibration on Breast Cancer Bone Metastasis and Vascularization in Mice. Calcif Tissue Int 111, 535–545 (2022). https://doi.org/10.1007/s00223-022-01009-4

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