Short telomeres correlate with a strong induction of cellular senescence in human dental follicle cells

Abstract

Background: Dental follicle cells (DFCs) are dental stem cells and interesting options for regenerative therapies in dentistry. However, DFCs acquire replicative senescence in long-Term cultures, but little is known about molecular processes. In previous studies, we observed that DFC cell lines become senescent at different rates. We hypothesized that short telomere length and increased DNA damage with genomic instability correlate with the accelerated induction of cellular senescence. Results: For this study we compared DFC cell lines that became senescent at different rates (DFC-F: strong senescent phenotype; DFC-S: weak senescent phenotype). The telomeres of DFC-F were shorter than those of the telomeres of DFC-S prior senescence. Interestingly, telomere lengths of both cell lines were nearly unchanged after induction of senescence. Gene expression analyses with genes associated with DNA damage before and after the induction of cellular senescence revealed that almost all genes in DFCs-F were down-regulated while the gene expression in DFC-S was almost constitutive. Moreover, number of aneuploid DFC-F were significantly higher after induction of cellular senescence. Conclusion: Our results supported our initial hypothesis that telomere length and genomic instability correlate with the accelerated induction of cellular senescence in DFC-F.