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. 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. Our results supported our initial hypothesis that telomere length and genomic instability correlate with the accelerated induction of cellular senescence in DFC_F.

中文翻译：

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端粒短与人类牙囊细胞强烈诱导细胞衰老相关

牙科卵泡细胞（DFC）是牙科干细胞，是牙科再生治疗的有趣选择。然而，DFCs在长期培养中具有复制衰老作用，但对分子过程所知甚少。在以前的研究中，我们观察到DFC细胞系以不同的速率衰老。我们假设端粒长度短和基因组不稳定性增加的DNA损伤与细胞衰老的加速诱导相关。在这项研究中，我们比较了以不同速率衰老的DFC细胞系（DFC_F：强衰老表型； DFC_S：弱衰老表型）。DFC_F的端粒短于DFC_S衰老前的端粒。有趣的是，诱导衰老后，两种细胞系的端粒长度几乎没有变化。基因表达分析与诱导细胞衰老前后的DNA损伤相关的基因表明，DFCs_F中的几乎所有基因均被下调，而DFC_S中的基因表达几乎是组成性的。此外，诱导细胞衰老后，非整倍体DFC_F的数量明显更高。我们的结果支持了我们最初的假设，即端粒长度和基因组不稳定性与DFC_F中细胞衰老的加速诱导相关。