Radiation-induced reduction of osteoblast differentiation in C2C12 cells

Therapeutic radiation causes bone damage and may increase fracture risks in treatment for head-andneck cancer and in pelvic irradiation. These properties can also be used for prevention of heterotopic ossification in hip arthroplasty. To evaluate the effects of ionizing radiation on osteoblast differentiation, C2C12 cells were directed into an osteogenic lineage by treatment with a combination of bone morphogenic protein 2 (BMP-2) (100 ng/ml) and heparin (30 mu g/ml) 6 h after irradiation (2 and 4 Gy). Osteoblast differentiation was evaluated based on alkali phosphatase (ALP) activity and expression of mRNA encoding ALP and collagen type I. Ionizing radiation suppressed the growth of C2C12 cells and decreased expression of ALP and collagen type I mRNAs with concomitant reduction of the ALP activity. Although further studies are needed to elucidate the molecular mechanism, our findings suggest that ionizing radiation at therapeutic doses interferes with bone formation by reducing ALP activity and expression of mRNA encoding ALP and collagen type I.