| Abstract [eng] |
Osteonecrosis of the jaw is a complication of long-term use of bisphosphonates which are used for the treatment of excessive bone resorption, hypercalcaemia. Also, there are other risk factors which stimulates the development of this disease, such as dental or periodontal diseases, glucocorticoid therapy, chemotherapy, smoking. However, pathogenesis of the disease is still not completely clear and there is no single effective treatment. Therefore, it is important to perform scientific research in order to better understand bisphosphonate-related mechanisms for osteonecrosis of the jaw development. That is what this project through addresses the role of osteoblasts in the disease model, which has been significantly less studied compared to osteoclasts, as bisphosphonate-related osteonecrosis of the jaw is known to be associated with induction of apoptosis in osteoblasts. This may be an important marker of early detection of the processes of osteonecrosis. The project further examined non-cellular regeneration therapy – the operation of exosomes that are isolated from adipose-type stem cells. The viability of osteoblasts treatment with different concentrations of bisphosphonates and isolated exosomes was investigated using spectrophotometric double-core staining methods. After executing experiments and summarizing the results, it was found that 5, 50 and 100 µM bisphosphonates cause statistically significant change for osteoblasts in terms of viability when compared to inactive cells. Also, incubation times of bisphosphonates after 48 and 72 hours were also statistically significant for osteoblast viability. Meanwhile, co-treatment of cells with both bisphosphonates and exosome samples showed a statistically significant increase compared to osteoblasts treated with bisphosphonates alone, with exosomes at a concentration of 10 µg / ml showing the best protective effect. In addition, studies of the energy profile of osteoblasts found that bisphosphonates markedly reduced mitochondrial and glycolytic activity. Meanwhile, stem cell exosomes partially reduced mitochondrial damage and did not affect glycolysis. The obtained results prove that fat-derived stem cell exosomes have a positive effect on the process of bone regeneration. |
