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Mechanisms of Radiation-Induced Bone Loss and Effect on Prostate Cancer Bone Metastases

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Annual summary rept. 1 Jun 2011 - 31 May 2012

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Patients with tumors in the pelvic region frequently receive radiation therapy, and as a result, bystander bone may experience adverse effects. Earlier reports demonstrated that radiation-induced bone loss occurs via increased osteoclast activation in a mouse model. Apoptosis of Osteocytes has been shown to trigger osteoclast progenitor recruitment and differentiation. We hypothesized that radiation induces osteocyte apoptosis leading to increased osteoclast formation and subsequent bone loss. We evaluated the effects of radiation on MLO-Y4 osteocytes, cell lines. Radiation with 2Gy dose dependently increased the number of trypan blue positive MLO-Y4 cells. We analyzed if the irradiated osteocytes can directly or indirectly stimulate osteoclast formation. We used the conditioned media of irradiated MLO-Y4 cells and treated them on RAW 264.7 cells and also co-cultured MLO-Y4 cells with RAW 264.7 cells and irradiated them using various doses of radiation. We used a single limb irradiation in-vivo model to demonstrate the effects of radiation on the hind limbs of 20 week old female C57Bl6 mice. There was no evidence that irradiated osteocytes could stimulate osteoclastic activity and osteoclastogenesis, either indirectly conditioned medium or directly co-culture. In the absence of other cell types, irradiation of RAW 264.7 osteoclast precursors already appeared to stimulate osteoclastic activity. We analyzed various bone parameters using microCT and histology TRAP stain, dynamic bone parameter. We also used TUNEL assay to analyze the amount of apoptosis radiation inflicted on the hind limbs. Radiation decreased the BVTV, ConnD and DA compared to the non-irradiated tibia. There was also significant increase of TRAP positive osteoclast per bone surface Oc.NmmBS on the irradiated tibia. The TUNEL assays for apoptotic osteocytes revealed significant increase of TUNEL positive osteocytes on the trabecular bone of the irradiated bone. In conclusion,

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  • Medicine and Medical Research

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