Gallic acid induces osteoblast differentiation and alleviates inflammatory response through GPR35/GSK3β/β‐catenin signaling pathway in human periodontal ligament cells

Abstract

AbstractBackground and ObjectiveGallic acid (GA) possesses various beneficial functions including antioxidant, anticancer, anti‐inflammatory as well as inhibiting osteoclastogeneis. However, effects on osteogenic differentiation, especially in human ligament periodontal (hPDL) cells, remain unclear. Thus, the aim of this study was to evaluate the function of GA on osteogenesis and anti‐inflammation in hPDL cells and to explore the involved underlying mechanism.MethodsPorphyromonas gingivalis lipopolysaccharide (Pg‐LPS) treatment was used as a model for periodontitis. ROS production was determined by H2DCFDA staining. Trans‐well and wound healing assays were performed for checking the migration effect of GA. Alizarin red and alkaline phosphatase activity (ALP) assays were performed to evaluate osteogenic differentiation. Osteogenesis and inflammatory‐related genes and proteins were measured by real‐time PCR and western blot.ResultsOur results showed that GA‐treated hPDL cells had higher proliferation and migration effect. GA inhibited ROS production‐induced by Pg‐LPS. Besides, GA abolished Pg‐LPS‐induced inflammation cytokines (il‐6, il‐1β) and inflammasome targets (Caspase‐1, NLRP3). In addition, GA promoted ALP activity and mineralization in hPDL cells, lead to enhance osteoblast differentiation process. The effect of GA is related to G‐protein‐coupled receptor 35 (GPR35)/GSK3β/β‐catenin signaling pathway.ConclusionGA attenuated Pg‐LPS‐induced inflammatory responses and periodontitis in hPDL cells. Taken together, GA may be targeted for therapeutic interventions in periodontal diseases.