Porphyromonas gingivalis triggers inflammatory responses in periodontal ligament cells by succinate-succinate dehydrogenase–HIF–1α axis

WenqiSu^abJiahongShi^aYunheZhao^aFuhuaYan^aLangLei^aHouxuanLi^a

^aNanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China^bCentral Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China

Abstract

Metabolic reprogramming from oxidative phosphorylation to glycolysis have been implicated in the pathogenesis of inflammatory diseases, such as pulmonary hypertension, rheumatoid arthritis and sepsis. Whether metabolic reprogramming participates in the progression of bacteriogenic periodontitis has never been reported. In the present study, we explored metabolic changes in periodontal ligament cells (PDLSCs) in response to Porphyromonas gingivalis. (P. gingivalis)-infected PDLSCs showed distinct metabolomics with metabolic reprogramming from oxidative phosphorylation to glycolysis. In addition, bacteria invasion triggered fundamental changes in glycolysis and tricarboxylate acid (TCA) cycle-related genes, such as the hexokinase (HK), isocitrate dehydrogenase (IDH) and succinate dehydrogenase (SDH). Moreover, P. gingivalis-infected PDLSCs showed accumulation of succinate, elevation in succinate dehydrogenase activity, pileup of reactive oxygen species and activation of hypoxia inducible factor-1α (HIF-1α) pathway. HIF-1α and succinate inhibitors, as well as SDH knockdown alleviated proinflammatory cytokine expression in P. gingivalis-infected PDLSCs. Therefore, targeting metabolic reprogramming by regulating the succinate-SDH–HIF–1α axis may facilitate host modulation therapy of chronic periodontitis.

Keywords

Succinate dehydrogenasePeriodontal diseasesBacteriaMetabolic reprogramming