gms | German Medical Science

Objectives: Particle therapy (PT), utilizing protons and carbon ions, presents a promising avenue for mitigating the adverse effects of radiation oncology, particularly in pediatric patients. Understanding the impact of PT on growing bone is crucial for optimizing its therapeutic potential. In this study, we employed an organotypic rat ex vivo femur culture model to explore the effects of PT.

Methods: Following irradiation, we conducted histological staining, immunohistochemical analyses, and gene expression profiling after one or 14 days of in vitro culture (DIV). Our investigation revealed notable findings regarding the influence of PT on bone physiology.

Results and conclusion: At 1 DIV, a significant decline in proliferating chondrocytes was observed, indicative of early cellular response to PT. However, at 14 DIV, we observed regenerative efforts characterized by the formation of chondrocytic clusters, suggesting a compensatory mechanism to restore bone integrity. Interestingly, accelerated mineralization was noted, accompanied by heightened proteoglycan production and secretion into the pericellular matrix, indicative of altered matrix dynamics post-PT exposure.

Analysis of gene expression patterns further elucidated the effects of PT on bone biology. Col2a1 expression, associated with collagen production, exhibited significant inhibition following PT, suggesting disrupted collagen synthesis pathways. Moreover, the decline in ColX expression over time was more pronounced in PT-treated specimens compared to non-irradiated controls, indicating perturbations in chondrocyte hypertrophy.

Key chondrogenic markers such as BMP2, RUNX2, and OPG, along with the osteogenic marker ALPL, demonstrated a significant reduction in their expression trajectory after 14 DIV in response to PT treatment. Notably, carbon ions exerted a stronger influence on gene expression compared to protons, underscoring the differential effects of particle types on bone biology.

In conclusion, our study contributes to a deeper understanding of the biological mechanisms underlying the impact of PT on bone tissue. By elucidating the interplay between PT and bone physiology, we provide valuable insights for refining therapeutic strategies and optimizing patient outcomes in radiation oncology, particularly in the context of pediatric care.