Effect of the gamma radiation and common antioxidants on some aspects of osteoblast differentiation during the formation of bone tissue in an in-vivo model

Gamma radiation is the emission of energy through short electromagnetic waves to a higher level of frequency with respect to ultraviolet light. This type of energy in the medical application is used as a tool to kill cancer cells in humans, however, adverse damages to its exposure can produce secondary effects in the short and long term depending on the damage in cells and tissues nearby to the irradiation zone, the human body will present various injuries and conditions. In bone tissue, secondary effects that have been observed, is an alteration of the architecture and integrity of bone extracellular matrix of cortical and trabecular tissue, which causes loss of bone density. However, the reason that the bone tissue is affected is not clear, but is believed to be related to the formation of free radicals, which generate oxidative damage in biomolecules of the cells, damaging the tissue structure, organs and systems of the human body. The studies to identify the main reasons that will affect bone tissue as a result of radiotherapy have been carried out by models In-vitro and some In-vivo. In most studies in-vitro with cells with osteoblast phenotype, the results suggest alterations in proliferation and differentiation of these cells. However, the etiology and the role of these changes in disorders and bone injuries as adverse secondary effects of the radiotherapy are very poorly understood to date. In the present study an In-vivo model was used, that are ectopic bone plates which are developed by endochondral ossification, after having implanted demineralized bone particles at 16 days of development, at which time they are constituted by bone tissue. Ectopic bone plates were used with the aim of knowing as gamma radiation indirectly modifies to cellular level the osteoblast differentiation, cells that are involved in the formation and mineralization of bone extracellular matrix. One of the well known effects of gamma radiation is the generation of free radicals, which may be involved in the etiology of the adverse secondary effects of radiotherapy observed in bone. Therefore we studied the role in the possible alteration of the differentiation of osteoblasts in In-vivo model mentioned above. The results show that gamma irradiation In-vivo decreases the synthesis of type I collagen, the most abundant protein of the extracellular bone matrix product of osteoblasts and expression of Runx2, specific gen of osteoblasts in differentiation, whereas that administration of antioxidants in the irradiated group on day 10 post-implant these alterations decreased clearly, not in the group with antioxidants irradiated on day 5 post-implant of the demineralized bone particles. We consider that this behavior is related to the level of vascularity present in the tissue at the moment of irradiation, allowing in the ectopic bone plates a major concentration of antioxidants that neutralized to the free radicals generated by radiation, protecting tissue. Additional studies are needed to confirm this explanation. The knowledge about the processes cellular and tissue underlying the adverse secondary effects in bones of radiotherapy help to design strategies to mitigate or reverse the changes in this tissue. (Author)