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. Electronic supplementary material The online version of this article (10.1186/s12860-019-0185-4) contains supplementary material, which is available to authorized users.

Effects of Cellular Senescence on Dental Follicle Cells

“…Previous studies on telomere length in dental pulp stem cells and induction of cellular senescence have shown similar results [33]. Interestingly, the telomeric erosion did not occur differently in the 2 cell lines during cell culture since almost no erosion was found for DFC_F and DFC_S in senescent DFCs [29]. Genomically higher rates of DNA damage and chromosome reorganization or aberration in DFC_F was the reason for the accelerated induction of cellular senescence.…”

“…Telomeric lengths of 5 DFC cell lines were almost similar, but 1 cell line had shorter telomeres. This cell line (DFC_F) with short telomeres was compared with another cell line with longer "standard" telomeres (DFC_S) [29]. Although we expect cells with shorter telomeres to have higher β-galactosidase activity than cells with longer telomeres, the opposite was observed in this study.…”

“…However, the original telomeric length of DFCs could be critical for induction of cellular senescence. A recent study compared telomer- ic length of 6 different isolations of DFCs [29]. Telomeric lengths of 5 DFC cell lines were almost similar, but 1 cell line had shorter telomeres.…”

“…Here, the cell morphology and the population doubling time did not change significantly. After passage 10 and in later stages of cell culture, however, cell proliferation decreased significantly and finally stopped [23, 29]. The appearance of longer population doubling times is associated with the induction of β-galactosidase activity in senescent cells.…”

Dental Follicle Cells: Roles in Development and Beyond

“…A previous study suggested that DFCs exhibited features of cellular senescence after being expanded after more than 14 cell passages, displaying decreased cell proliferation, enlarged cell size, and upregulated expression of β -galactosidase [137]. Short telomeres and increased DNA damage with genomic instability were correlated with the accelerated induction of cellular senescence [138]. Moreover, the osteogenic differentiation of DFCs was inhibited due to cellular senescence, followed with a lower extent to differentiate into biomineralizing cells [137].…”