X-ray radiation at low doses stimulates differentiation and mineralization of mouse calvarial osteoblasts

Radiotherapy is considered to cause detrimental effects on bonetissue eventually increasing bone loss and fracture risk. However,there is a great controversy on the real effects of irradiation itselfon osteoblasts, and the mechanisms by which irradiation affectsosteoblast differentiation and mineralization are not completelyunderstood. We explored how X-ray radiation influences differentiationand bone-specific gene expression in mouse calvarialosteoblasts. Irradiation at 2 Gy not only increased differentiationand mineralization of the cells, but also upregulated the expressionof alkaline phosphatase, type I collagen, osteopontin,and osteocalcin at early stages of differentiation. However, irradiationat higher doses (＞2 Gy) did not stimulate osteoblast differentiation,rather it suppressed DNA synthesis by the cells withouta toxic effect. Additional experiments suggested that transforminggrowth factor-beta 1 and runt-transcription factor 2 play importantroles in irradiation- stimulated bone differentiation by acting asupstream regulators of bone-specific markers.