Department of General Dentistry, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
Department of Orthodontics, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
Mol Med Rep. 2019 May;19(5):3649-3657. doi: 10.3892/mmr.2019.10027. Epub 2019 Mar 14.
Periodontal ligament stem cells (PDLSCs) are promising stem cells sources for regenerative medicine, particularly clinical periodontal ligament repair. It is critical to maintain high quality and a large quantity of PDLSCs for clinical usage. However, how PDLSCs respond to environmental stimuli, including reactive oxygen species (ROS), is poorly understood. The aim of the present study was to investigate how PDLSCs react to oxidative stress and the underlying mechanisms. Hydrogen peroxide‑induced oxidative stress was used to mimic a ROS increase in rat PDLSCs. The expression levels of Creb were detected under oxidative stress to examine the role that Creb serves in PDLSCs under oxidative stress. The present results demonstrated that the expression of Creb was reduced in a dose‑dependent manner in response to the H2O2 stimulus. Overexpressing Creb significantly reduced the ROS levels and protein expression levels of apoptotic genes in PDLSCs. The phosphorylation of the ERK pathway is indispensable in the activation of Creb‑induced protection. Our results revealed a protective role of Creb in ROS‑induced apoptosis, and validated the ERK/Creb/apoptosis regulator Bcl‑2 pathway works as an anti‑apoptotic signaling in PDLSCs. These findings will facilitate the in vitro culturing of PDLSCs for clinical usage and promote stem cell based therapy for periodontal tissue regeneration.
牙周膜干细胞（PDLSCs）是再生医学中很有前途的干细胞来源，特别是在临床牙周膜修复方面。对于临床应用而言，维持高质量和大量的 PDLSCs 至关重要。然而，PDLSCs 如何对环境刺激（包括活性氧（ROS））作出反应，目前还知之甚少。本研究旨在探讨 PDLSCs 对氧化应激的反应及其潜在机制。使用过氧化氢诱导的氧化应激来模拟 ROS 在大鼠 PDLSCs 中的增加。在氧化应激下检测 Creb 的表达水平，以研究 Creb 在氧化应激下对 PDLSCs 所起的作用。本研究结果表明，Creb 的表达水平随 H2O2 刺激呈剂量依赖性降低。过表达 Creb 可显著降低 PDLSCs 中的 ROS 水平和凋亡基因的蛋白表达水平。ERK 通路的磷酸化在 Creb 诱导的保护中是不可或缺的。我们的研究结果揭示了 Creb 在 ROS 诱导的细胞凋亡中的保护作用，并验证了 ERK/Creb/凋亡调节因子 Bcl-2 通路在 PDLSCs 中作为一种抗凋亡信号通路发挥作用。这些发现将有助于 PDLSCs 的体外培养用于临床应用，并促进基于干细胞的牙周组织再生治疗。
