Zusammenfassung
Objective: Short telomeres and genomic DNA damage are causes of cellular senescence in dental follicle cells (DFCs). Design: This study examined the role of the DNA damage response (DDR) during cellular senescence of DFCs by beta-galactosidase activity and DNA damage by comet assay. Expression of genes/proteins was determined by Western Blots and reverse transcription-quantitative polymerase ...
Zusammenfassung
Objective: Short telomeres and genomic DNA damage are causes of cellular senescence in dental follicle cells (DFCs). Design: This study examined the role of the DNA damage response (DDR) during cellular senescence of DFCs by beta-galactosidase activity and DNA damage by comet assay. Expression of genes/proteins was determined by Western Blots and reverse transcription-quantitative polymerase chain reaction, while glycolysis was enzymat-ically estimated. Cell cycle stages and reactive oxygen species (ROS) were investigated by flow cytometry. Results: During the induction of cellular senescence gene expression of DDR genes were down-regulated, while DNA double-strand breaks occurred at the same time. Furthermore, inhibition of DNA protein kinase (DNA-PK) reduced senescence and ROS, both of which are associated with cellular senescence. In contrast, while these data suggest that inhibition of DDR is associated with the induction of cellular senescence, inhibition of DNA-PK did not result in renewal of DFCs, as inhibition resulted in typical features of depleted cells such as increased cell size and reduced cell proliferation rate. DNA-PK repression inhibited both osteogenic differentiation potential and glycolysis, which are typical features of cellular exhaustion. Moreover, DNA-PK affects cellular senescence via activation of AKT1 (protein kinase B). Conclusion: Our results suggest that DNA-PK promotes cellular senescence, but DFCs may control the induction of cellular senescence via down-regulation of DDR genes. However, we also showed that inhibition of DNA-PK cannot renew senescent DFCs
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