Nrf2 Inhibits Periodontal Ligament Stem Cell Apoptosis under Excessive Oxidative Stress

Abstract

The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis oxidative microenvironment. We created an oxidative stress model with H2O2-treated PDLSCs. We used real-time PCR, Western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the function of nuclear factor-erythroid 2-related factor 2 (Nrf2). We demonstrated that with upregulated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), the effect of oxidative stress was obvious under H2O2 treatment. Oxidative molecules were altered after the H2O2 exposure, whereby the signaling of Nrf2 was activated with an increase in its downstream effectors, heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1) and γ-glutamyl cysteine synthetase (γ-GCS). Additionally, the apoptosis levels gradually increased with oxidative stress by the upregulation of caspase-9, caspase-3, Bax and c-Fos levels in addition to the downregulation of Bcl-2. However, there was no alterations in levels of caspase-8. The enhanced antioxidant effect could not mitigate the occurrence of apoptosis. Furthermore, Nrf2 overexpression effectively improved the anti-oxidative levels and increased cell proliferation. At the same time, overexpression effectively restrained TUNEL staining and decreased the molecular levels of caspase-9, caspase-3, Bax and c-Fos, but not that of caspase-8. In contrast, silencing the expression of Nrf2 levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its effects on regulating oxidative stress and anti-intrinsic apoptosis by the activation of oxidative enzymes.

Nrf2/ARE pathway attenuates oxidative and apoptotic response in human osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling axis

“…Our results showed that Nrf2 over-expression effectively diminished TUNEL staining, reduced PARP cleavage and decreased the activation of Caspase-3, Caspase-8, and Caspase-9 in IL-1β-stimulated OA chondrocytes (Figure 5B, C and 6A). A recent report demonstrated that Nrf2 activation exerts anti-apoptotic effects by upregulating the levels of Bcl-2, in addition to downregulating Bax and c-fos expression in a different cell type [67]. In agreement with this study, we found that Nrf2 over-expression inhibited the expression of pro-apoptotic proteins Bax, Bad and Bid and upregulated the expression of anti-apoptotic proteins Bcl2, Bcl-xl and Mcl-1 in IL-1β-stimulated human OA chondrocytes (Supplementary Figure 5C).…”

Enhanced Oxidative Damage and Nrf2 Downregulation Contribute to the Aggravation of Periodontitis by Diabetes Mellitus

“…Downregulation of Nrf2 and subsequent inhibition of antioxidant production have been associated with more advanced periodontitis [7]. In addition, Nrf2 overexpression has been proved to activate antioxidative enzymes and thus effectively inhibit periodontal ligament stem cell apoptosis in the local oxidative stress microenvironment of periodontitis [8]. Moreover, Nrf2 also plays important roles in DM-related diseases [9].…”

Does subgingival bacterial colonization differ between implants and teeth? A systematic review

“…During the manual search, no additional articles were selected. Eight articles were excluded after full-text reading: six articles did not directly compare microbiological data from healthy teeth with healthy implants, or periodontitis and peri-implantitis 5,7,9,13,14,15,16 and two studies did not present statistical analysis comparing periodontal and peri-implant health or disease (Table 2). 17,18 Therefore, 8 articles were included in the current systematic review.…”