Inhibition of lyosphosphatidic acid receptor 1 signaling in periodontal ligament stem cells reduces inflammatory paracrine effect in primary astrocyte cells

ABSTRACT

Lysophosphatidic acid (LPA) is a bioactive lipid messenger involved in the pathogenesis of chronic inflammation and various diseases. Recent studies have shown an association between periodontitis and neuroinflammatory diseases such as Alzheimer’s disease, stroke, and multiple sclerosis. However, the mechanistic relationship between periodontitis and neuroinflammatory diseases remains unclear. The current study found that lysophosphatidic acid receptors 1 (LPAR1) and 6 (LPAR6) exhibited increased expression in primary microglia and astrocytes. The primary astrocytes were then treated using medium conditioned to mimic periodontitis through addition of Porphyromonas gingivalis lipopolysaccharides, and an increased nitric oxide (NO) production was observed. Application of conditioned medium from human periodontal ligament stem cells with or without LPAR1 knockdown showed a decrease in the production of NO and expression of inducible nitric oxide synthase and interleukin 1 beta. These findings may contribute to our understanding of the mechanistic link between periodontitis and neuroinflammatory diseases.