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.
INTRODUCTION
Radiotherapy, either alone or in combination with surgery, is one of the most common approaches for oncologic treatment. Nearly 10 million cancer patients worldwide (approximately half of new cancer cases per year) are estimated to undergo radiotherapy annually (1). The rapid development of radiotherapy techniques is continuously prolonging the survival time of patients and increasing the cure rate of malignant tumors (for example, the 10-year survival rates of prostate cancer and breast cancer have reached ~95 and 85%, respectively) (2, 3), and radiotherapy-related adverse effects have received increasing attention. The skeleton has the capacity to absorb much more radiation energy than other tissues, owing to its higher mineral component content, while radiotherapy-induced bone damage also remains a common and tough clinical issue (4, 5). Radiation-induced bone damage includes the rapid loss of bone mass, increased bone fragility and susceptibility to fractures, and elevated risks of osteonecrosis in the radiation field (6). Clinical data suggest that approximately 20% of breast cancer patients experience pathologic rib fractures after radiotherapy (7, 8). Pelvic fractures were noted in 16 to 37% of cervical cancer patients following focal radiotherapy (9, 10). Moreover, focal radiotherapy has been found to induce a progressive systemic decrease in bone mineral density (BMD) in cancer patients (11, 12). Considering that most cancer patients are middle-aged or older and may suffer from various primary diseases (e.g., osteoporosis and diabetes), radiotherapy aggravates the risks of fragility fractures and osteonecrosis and subsequent challenges of medical care.
Link to full article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401628/
