The relationship between radiosensitivity and expression of micro RNAs in murine osteoblastic cell exposed to high dose rate alpha particles

Osteoblastic cells in the bone marrow produce the bone matrix, participate in mineralization of bone and regulate the balance of calcium and phosphate ions in the developing bone. In addition, the radiosensitive hematopoietic stem/progenitor cells form a niche with osteoblastic cells to maintain immature state and self-renewal in the bone marrow microenvironment. In the field of radiotherapy, internal radiotherapy using radioactive isotopes that emit alpha particles is performed, and antitumor effect is expected by radioisotopes (such as 223-Ra) when the primary cancer cells metastasize to bone marrow. A major problem in this treatment is that the efficacy and side effects form show a high degree of individual variability, and the response of a patient is very difficult to predict. The mechanisms of the variability are not known, but it is possible that some contributing factors are the alpha radiation-induced modulation of osteoblastic cell activity. However, the characteristics of micro-RNA expressions in alpha-irradiated osteoblastic cells remain unclear. The purpose of this study is to clarify the pattern of miRNA expressions in osteoblast derived from freshly bone marrow cells exposed to alpha particle radiation. Murine bone marrow cells from both femurs were differentiated to osteoblastic cells using cell culture medium and exposed to 0-1 Gy of alpha radiation. The 24 miRNAs were significantly up- or down-regulated: mmu-let-7a-5p, mmu-let-7b-5p, mmu-let-7c-5p, mmu-miR-1224-5p, mmu-miR-125b-5p, mmu-miR-296-5p, mmu-miR-331-3p, mmu-miR-3473b, mmu-miR-3960, mmu-miR-3963, mmu-miR-466i-5p, mmu-miR-494-3p, mmu-miR-5126, mmu-miR-6360, mmu-miR-6366, mmu-miR-6378, mmu-miR-6769b-5p, mmu-miR-6937-5p, mmu-miR-7005-5p, mmu-miR-7042-5p, mmu-miR-7047-5p, mmu-miR-709, mmu-miR-8110, mmu-miR-8117). These results indicate that exposure of osteoblastic cells to alpha particles leads to unique expression of miRNAs and it may give the cell radiosensitive environment. The pattern of micro RNA expressions in osteoblastic cell derived from freshly bone marrows exposed to 0.5 Gy or 1 Gy alpha particles (0.22 Gy/min) was analyzed using micro RNA microarray. The data analysis had been performed triplicate samples.