Vibration-Mediated Recovery of Irradiated Osteocytes and Their Regulatory Role in Breast Cancer Bone Metastasis.

Abstract

Radiotherapy is a cornerstone of breast cancer treatment, but it can unintentionally damage bone, causing bone loss and pain, with no currently effective therapeutic strategy available. While chemically mediated radioprotection is extensively studied, mechanically mediated radioprotection remains underexplored. Given its safety and efficacy, this work examines the potential of low-magnitude, high-frequency (LMHF) vibration as a non-invasive intervention to protect irradiated bone, focusing on osteocytes-the primary mechanosensors and regulators whose functions extend to modulating breast cancer bone metastasis. These results demonstrate that LMHF vibration (0.3 g, 60 Hz, 1 h) mitigates osteocyte apoptosis and upregulates cytoskeletal markers following 8 Gy irradiation. LMHF vibration applied 1 h per day over 3 days restores the regulatory function of irradiated osteocytes in controlling breast cancer extravasation in a microfluidic platform. A combined approach integrating vibration with radiotherapy further reduces cancer invasion and extravasation, demonstrating a compound effect. RNA sequencing (RNA-seq) analysis reveals that this osteocyte-mediated regulation is possibly driven by the Wnt signaling pathway. These findings highlight the potential of LMHF vibration in enhancing radiotherapy efficacy by protecting osteocytes and reducing breast cancer metastasis, underscoring the promise of a non-invasive mechanical intervention in preserving bone health and optimizing cancer treatment outcomes.