High-specificity protection against radiation-induced bone loss by a pulsed electromagnetic field

Author: Zedong Yan1, Dan Wang1, Jing Cai2, Liangliang Shen3, Maogang Jiang1, Xiyu Liu1, Jinghui Huang4, Yong Zhang5, Erping Luo1, Da Jing1,6,7
1 Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.
2 College of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang, China.
3 The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
4 Institute of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
5 Department of Pulmonary and Critical Care of Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
6 The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Fourth Military Medical University, Xi'an, China.
7 Shaanxi Provincial Key Laboratory of Bioelectromagnetic Detection and Intelligent Perception, Fourth Military Medical University, Xi'an, China.
Conference/Journal: Sci Adv
Date published: 2022 Aug 26
Other: Volume ID: 8 , Issue ID: 34 , Pages: eabq0222 , Special Notes: doi: 10.1126/sciadv.abq0222. , Word Count: 159

Radiotherapy increases tumor cure and survival rates; however, radiotherapy-induced bone damage remains a common issue for which effective countermeasures are lacking, especially considering tumor recurrence risks. We report a high-specificity protection technique based on noninvasive electromagnetic field (EMF). A unique pulsed-burst EMF (PEMF) at 15 Hz and 2 mT induces notable Ca2+ oscillations with robust Ca2+ spikes in osteoblasts in contrast to other waveforms. This waveform parameter substantially inhibits radiotherapy-induced bone loss by specifically modulating osteoblasts without affecting other bone cell types or tumor cells. Mechanistically, primary cilia are identified as major PEMF sensors in osteoblasts, and the differentiated ciliary expression dominates distinct PEMF sensitivity between osteoblasts and tumor cells. PEMF-induced unique Ca2+ oscillations depend on interactions between ciliary polycystins-1/2 and endoplasmic reticulum, which activates the Ras/MAPK/AP-1 axis and subsequent DNA repair Ku70 transcription. Our study introduces a previously unidentified method against radiation-induced bone damage in a noninvasive, cost-effective, and highly specific manner.

PMID: 36001662 PMCID: PMC9401628 DOI: 10.1126/sciadv.abq0222