LPS-induced inflammation potentiates dental pulp stem cell odontogenic differentiation through C5aR and p38.

Abstract

Aim: Inflammation is a complex host response to harmful infection or injury, and it seems to play a crucial role in tissue regeneration both positively and negatively. We have previously demonstrated that the activation of the complement C5a pathway affects dentin-pulp regeneration. However, limited information is available to understand the role of the complement C5a system related to inflammation-mediated dentinogenesis. The aim of this study was to determine the role of complement C5a receptor (C5aR) in regulating lipopolysaccharide (LPS)-induced odontogenic differentiation of dental pulp stem cells (DPSCs).

Material and methods: Human DPSCs were subjected to LPS-stimulated odontogenic differentiation in dentinogenic media treated with the C5aR agonist and antagonist. A putative downstream pathway of the C5aR was examined using a p38 mitogen-activated protein kinase (p38) inhibitor (SB203580).

Results: Our data demonstrated that inflammation induced by the LPS treatment potentiated DPSC odontogenic differentiation and that this is C5aR dependent. C5aR signaling controlled the LPS-stimulated dentinogenesis by regulating the expression of odontogenic lineage markers like dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP-1). Moreover, the LPS treatment increased the total p38, and the active form of p38 expression, and treatment with SB203580 abolished the LPS-induced DSPP and DMP-1 increase.

Conclusions: These data suggest a significant role of C5aR and its putative downstream molecule p38 in the LPS-induced odontogenic DPSCs differentiation. This study highlights the regulatory pathway of complement C5aR/p38 and a possible therapeutic approach for improving the efficiency of dentin regeneration during inflammation.