TPPU inhibits inflammation-induced excessive autophagy to restore the osteogenic differentiation potential of stem cells and improves alveolar ridge preservation

作者：Haixia Dang, Weixian Chen, Lan Chen, Xinru Huo, Fu Wang · 发表于：Scientific Reports · 年份：2023 · DOI：10.1038/s41598-023-28710-0 · 被引用次数：16 · 研究领域：Eicosanoids and Hypertension Pharmacology、Alcohol Consumption and Health Effects、Heme Oxygenase-1 and Carbon Monoxide

Inflammation-induced autophagy is a double-edged sword. Dysfunction of autophagy impairs the differentiation capacity of mesenchymal stem cells and enhances inflammation-induced bone loss. Tooth extraction with periodontal and/or endodontic lesions exacerbates horizontal and vertical resorption of alveolar bone during the healing period. Alveolar socket preservation (ASP) procedure following tooth extraction has important clinical implications for future prosthodontic treatments. Studies have shown that epoxyeicosatrienoic acids (EETs) have significant anti-inflammatory effects and participate in autophagy. However, whether EETs can minimize alveolar bone resorption and contribute to ASP by regulating autophagy levels under inflammatory conditions remain elusive. Here, we figured out that LPS-induced inflammatory conditions increased the inflammatory cytokine and inhibited osteogenic differentiation of human dental pulp stem cells (hDPSCs), and led to excessive autophagy of hDPSCs. Moreover, we identified that increased EETs levels using TPPU, a soluble epoxide hydrolase inhibitor, reversed these negative outcomes. We further demonstrated the potential of TPPU to promote early healing of extraction sockets and ASP, and speculated that it was related to autophagy. Taken together, these results suggest that targeting inhibition of soluble epoxide hydrolase using TPPU plays a protective role in the differentiation and autophagy of mesenchymal stem cells and provides potential fe...