Abstract
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.