In vitro effects of radiation and mechanical load on murine osteocytes MLO-Y4

The increased survival rates for cancer as a result of improved diagnosis and treatment has come with the drawback that cancer treatment side effects are becoming more frequent as well. Cancer treatment induced bone loss can be caused by a variety of different treatment regimes, one of these being radiotherapy. Previously most research on the effects of radiation on bone tissue has focussed on the bone synthesizing osteoblasts and the bone resorbing osteoclasts. In the first part of this study, the effects of radiation on osteocyte survival and gene expression is investigated using the MLO-Y4 osteocyte cell line. A growing body of evidence shows that mechanical loading of the bones has a positive effect on bone health and bone strength. It is therefore hypothesised that mechanical loading could play a role in the prevention of radiation induced bone loss. In the second part of this study, the combined effect of radiation and mechanical load on osteocyte survival and gene expression has been investigated using a fluid flow shear stress system to mimic mechanical loading of the osteocytes. It was shown that a radiation dose of 5 Gy induces apoptosis within 24 to 48 hours and increased RANKL expression. Fluid flow shear stress was shown to decrease apoptosis following radiation and decrease the RANKL:OPG gene expression while increasing Bcl2:Bax gene expression. Taken together, these findings seem to support the hypothesis that mechanical loading of bones may help in the protection against radiation induced bone loss, by reducing osteocyte apoptosis