Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
Differentiation. 2020 Jul-Aug;114:20-26. doi: 10.1016/j.diff.2020.05.003. Epub 2020 May 18.
Replicative senescence causes a reduced osteogenic differentiation potential of senescent dental follicle cells (DFCs). The transcription factor p53 is often involved in the induction of cellular senescence, but little is known about its role in DFCs. This study examined for the first time the role of p53 compared to its pro-proliferative antagonist E2F-1 in terms of osteogenic differentiation potential and induction of senescence. Protein expression of E2F-1 decreased during cell aging, while p53 was expressed constitutively. Gene silencing of E2F1 (E2F-1) inhibited the proliferation rate of DFCs and increased the induction of cellular senescence. The induction of cellular senescence is regulated independently of the gene expression of TP53 (p53), since its gene expression depends on the expression of E2F1. Moreover, gene silencing of TP53 induced E2F1 gene expression and increased cell proliferation, but did not affect the rate of induction of cellular senescence. TP53 knockdown further induced the alkaline phosphatase and mineralization in DFCs. However, the simultaneous silencing of TP53 and E2F1 did not inhibit the inductive effect of TP53 knockdown on osteogenic differentiation, indicating that this effect is independent of E2F-1. In summary, our results suggest that p53 inhibits osteogenic differentiation and cell proliferation in senescent DFCs, but is not significantly involved in senescence induction.
复制性衰老会降低衰老的齿槽突细胞（DFC）的成骨分化潜能。转录因子 p53 通常参与细胞衰老的诱导，但关于其在 DFC 中的作用知之甚少。本研究首次研究了 p53 与其促有丝分裂拮抗剂 E2F-1 相比在成骨分化潜能和衰老诱导方面的作用。E2F-1 的蛋白表达在细胞衰老过程中减少，而 p53 则持续表达。E2F1（E2F-1）的基因沉默抑制了 DFC 的增殖率并增加了细胞衰老的诱导。细胞衰老的诱导独立于 TP53（p53）的基因表达调控，因为其基因表达依赖于 E2F1 的表达。此外，p53 的基因沉默诱导了 E2F1 的基因表达并增加了细胞增殖，但不影响细胞衰老的诱导率。p53 敲低进一步诱导了 DFC 中的碱性磷酸酶和矿化。然而，TP53 和 E2F1 的同时沉默并没有抑制 p53 敲低对成骨分化的诱导作用，表明这种作用独立于 E2F-1。总之，我们的结果表明，p53 抑制衰老的 DFC 中的成骨分化和细胞增殖，但在衰老诱导中没有明显参与。
