Identification of a Secreted Osteoclastogenic Factor in Irradiated Pre-Osteoclast Cells

The mechanism of bone degradation in response to aging has been the focus of many osteoporosis studies. However, there are other factors that contribute to bone degradation, including radiation. People exposed to abnormally high levels of radiation, including astronauts and cancer patients undergoing radiation therapy, have an increased risk of osteoporosis. However, the mechanism by which this occurs is unknown. It has been shown in vitro that the pre-osteoclast cell line RAW 264.7 secretes osteoclastogenic factors in response to radiation, but the factors have yet to be identified. My goal is two fold— first, determine if primary pre-osteoclasts mimic this event, and second, identify the osteoclast-producing factors. Preliminary results have shown that primary pre-osteoclast cells may be producing an osteoclast-producing factor in response to radiation— however, replication of the experiment will be done to confirm these results. In order to achieve the second goal, I will use a cytokine array to measure the concentration of potential factors, and observe if there is a difference in concentration between medium from irradiated cells and non-irradiated cells. The results of the array will then be confirmed by successfully mimicking the effect of radiation by controlling the concentration of the factor added to naïve pre-osteoclast cells. Once the factor is identified, it may bring scientists closer to the elucidation of the mechanism by which radiation induced osteoclastogenesis and bone degradation occurs. If the mechanism is known, this might allow for more specialized therapies that could slow or even stop the progression of this disease.