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Evaluation of zoledronate and bioactive compounds in mesenchymal stem cells extracted from deciduous teeth.


The osteonecrosis of the jaw is often a reported clinical complication in patients who are medicated with bisphosphonates (such as zoledronate – ZOL) for bone pathologies. However, the use of bioactive compositions is being a promising strategy used in the regeneration of lost tissue.

Objetivos - Metodologia - Resultados - Discussão dos Resultados/Objectives - Methodology - Results - Discussion of Results/Objetivos - Metodología - Resultados - Discusión de los resultados

Therefore, the main aim of the study has been to evaluate in mesenchymal stem cells (MSCs), the cellular viability after treatment with ZOL and bioactive compositions. The MSCs were treated with ZOL in different concentrations (2.5, 5 or 10 μM for 1 day and 1, 3, 5 or 10 μM for 4 days) and with bioactive compositios such as ascorbic acid-2 phosphate (ASAP) (172 μM), sodium fluoride (NaF) (50 μM) and glycine (10 μM) for 4 days. Furthermore, the bioactive compositions that showed the best cellular viability was tested for cytoprotective potential after ZOL treatment. The viability evaluation was performed through the test (bromide of 3- (4,5- dimethylthiazol-2-yl) –2,5- diphenyltetrazolium) (MTT) after the treatments. The results of the cells treated with ZOL showed no statistically significant difference in every concentration in a 1 day period (F (3.49)= 0.587; p=0.63). The results of the average absorbance ± standard deviation (SD), related to cell viability after 1 day of ZOL treatment were: 0.279 ± 0.046 for the control group, 0.297 ± 0.040 for the 2.5 μM, 0.294 ± 0.038 for the 5 μM and 0.292 ± 0.028 for the 10 μM. After 4 days, there was a significant statistical difference in every concentrations relative to the control; the results of the average absorbance ± SD were: 0.336 ± 0.045 for the control group, 0.224 ± 0.029 for the 1 μM (p<0.01), 0.212 ± 0.012 for the 3 μM (p<0.01), 0.188 ± 0.057 for the 5 μM (p<0.01) and 0.084 ± 0.026 for the 10 μM (p<0.01). Among the bioactive compositions, ASAP was the only one that significantly increased the MSCs viability. The glycine demonstrated a decrease in the cell viability. After 4 days, the average absorbance ± SD were: 0.396 ± 0.050 for the control, 0.461 ± 0.039 for the ASAP (p<0.05), 0.360 ± 0.039 for the NaF (p=ns) and 0.332 ± 0.025 for the glycine (p<0.01). The cells treated with ASAP were statistically different from the glycine and NaF (ps<0.01). However, although only ASAP increased the cellular viability when associated with ZOL, it demonstrated an absorbance increase, but did not demonstrate the cytoprotective feature in the concentration used, with 0.188 ± 0.057 being the the average absorbance ± SD for cells treated with 5 μM of ZOL and 0.233 ± 0.053 for 5 μM of ZOL+ASAP (p>0.05).

Considerações Finais/Final considerations/Consideraciones finales

Furthermore, it is suggested that ascorbic acid is a promising bioactive compositions for the tissue regeneration, although it does not protect against the cytotoxicity of the studied drug.

Acknowledgements: MCTIC, FINEP, CNPq, Stem Cell Research Institute (IPCT).

Palavras-chave/Key words/Palabras clave

stem cells, bifosfonates, osteonecrosis, bioactive compositions.


Mesenchymal stem cells/adultas


GABRIELA MORAES MACHADO, Rafaela Hartmann Kasper, Natasha Maurmann, Myrian Camara Brew, Marcos do Couto, André Wiltgen, Célia Regina Winck Mahl, Caren Serra Bavaresco, Patrícia Pranke