Cellular responses of osteoblastic and osteocyte-like cell lines after exposure to ionizing radiation

Abstract

Bone demineralization during space travel is a well known phenomenon seen in astronauts especially on long term missions. Besides altered gravity conditions, radiation exposure is considered to be one of the major health hazards. Until now, little is known about the effects of space radiation on the skeletal system and its contribution to the pathologies of bone loss during space flight. Here, we examined the impact of ionizing radiation on osteoblastic (OCT-1) and osteocyte-like (MLO-Y4) cell lines regarding cell cycle progression and apoptosis induction. Osteocytes encompass terminally differentiated osteoblasts and exist embedded in the mineralized matrix, residing individually in caves called lacunae. How osteocytes and osteoblasts respond to different kinds of stress, like exposure to ionizing radiation is widely unknown. Previous studies report that viable osteocytes prevent osteoclast activation and that dying or apoptotic osteocytes send signals to recruit osteoclasts. Current findings suggest that apoptotic osteocytes might affect osteoclastic activity. Cellular exposure to X-irradiation might therefore be a contributor, influencing the process of bone formation and bone resorption. In this work, the detection of apoptotic cells was performed via DNA-DAPI staining, to detect apoptotic cells, which display distinct membrane blebbing and the formation of apoptotic bodies. The induction of apoptotic bodies was associated with a dose dependent inhibition of cell cycle progression in both cell lines. Increased Caspase 3 activity could be detected within 24 h after exposure, which could be directly correlated to the received radiation dose. Our results indicate that exposure to X-irradiation could result in a radiation-induced cell cycle arrest which may trigger cellular apoptosis. However, even if a cell survives the initial radiation damage, attenuation in the differentiation and mineralization potential may lead to severe damage, in particularly regarding osteogenic bone diseases like osteoporosis.