Periostin regulates LPS‐induced apoptosis via Nrf2/HO‐1 pathway in periodontal ligament fibroblasts

Abstract

Objective: Periostin is important for the maintenance of periodontal tissue, but its role in periodontitis is controversial. This research investigated the effect of periostin in periodontitis and the underlying mechanism. Design: Mouse periodontitis models in vivo and inflammation model in vitro which were induced by Porphyromonas gingivalis lipopolysaccharide were established to evaluate periostin expression. Human periodontal ligament fibroblasts (PDLFs) were treated with lipopolysaccharide and N-acetylcysteine, fluorescence staining, flow cytometry, Western blot, and qRT-PCR were used to detect reactive oxygen species (ROS), periostin expression, and apoptosis-related makers. The periostin gene was successfully transfected into PDLFs to verify the effect of periostin on apoptosis. Then, the Nrf2 inhibitor was added to clarify the mechanism. Results: Periostin expression decreased in the periodontal ligaments of mouse periodontitis models and lipopolysaccharide-induced PDLFs. Lipopolysaccharide promoted the activation of ROS and apoptosis in PDLFs, whereas N-acetylcysteine reversed this condition. Overexpression of periostin suppressed apoptosis of PDLFs and reversed the inhibitory effect of lipopolysaccharide on nuclear Nrf2 expression. Moreover, the Nrf2 inhibitor attenuated the protective effect of periostin on lipopolysaccharideinduced apoptosis. Conclusions: Lipopolysaccharide induced apoptosis in PDLFs by inhibiting periostin expression and thus Nrf2/HO-1 pathway, indicating that periostin could be a potential therapeutic target for periodontitis.

Melatonin-Derived Carbon Dots with Free Radical Scavenging Property for Effective Periodontitis Treatment via the Nrf2/HO-1 Pathway

“…As a critical enzyme in heme degradation, HO-1 functions as an antioxidant and antiinflammatory agent, providing protection to tissues. 53 Our findings demonstrate that the transcriptional activity of Nrf2 and HO-1 genes is suppressed by the presence of ROS. This inhibition is closely linked to the antioxidant capacity of organisms, signifying that severe oxidative stress can undermine the antioxidant capacity of organisms.…”

“…This relocation enables the transcription of downstream antioxidative genes, among them HO-1. As a critical enzyme in heme degradation, HO-1 functions as an antioxidant and anti-inflammatory agent, providing protection to tissues …”

The effect of Nrf2 on bone resorption in chronic apical periodontitis

“…Studies have shown that periodontal tissue damage in Nrf2 knockout mice is more serious than that in wild-type mice [42], indicating that Nrf2 may have a protective effect on bone against damage caused by periodontitis. It has been suggested that the Nrf2 antioxidant defense pathway may be activated under oxidative stress induced by experimental periodontitis [43,44].…”

Programmed cell death of periodontal ligament cells

“…The LPS derived from Porphyromonas gingivalis induce the apoptosis of human periodontal ligament fibroblasts by increasing the levels of cytochrome c and activating caspase‐3 (Seo et al, 2012). In addition, LPS can induce the apoptosis of periodontal ligament fibroblasts by inhibiting the expression of BMP and subsequently suppressing the nuclear factor erythroid‐2‐related factor 2/heme oxygenase1 (Nrf2/HO‐1) pathway (Jiang, Yang, et al, 2022). Interestingly, the overexpression of Sirt1 significantly increased cell viability in LPS‐damaged periodontal ligament fibroblasts by reducing the release of pro‐inflammatory cytokines (IL‐1α, IL‐6, IL‐8, and TNF‐α), downregulating TLR4 expression, and inhibiting the JNK/nuclear factor kappa‐B (NF‐κB) pathway to decrease apoptosis (Li et al, 2018).…”