Porphyromonas gingivalis is associated with endodontic pulpitis, causing damage to the dental pulp, leading to severe pain and a decline in quality of life. Regenerative pulp treatments using dental pulp stem cells (DPSCs) can be hindered by interactions between DPSCs and the infecting bacteria. The protein WNT family member 4 (Wnt4) plays a critical role in the differentiation of DPSCs and the regeneration of odontogenic tissue. However, the specific influence of P. gingivalis on Wnt4 remains unclear. In this study, we employed a computational approach to investigate the underlying mechanisms through which P. gingivalis-produced metabolites inhibit the Wnt4 protein, thereby diminishing the regenerative potential and therapeutic efficacy of odontogenic tissue. Among the metabolites examined, C29H46N7O18P3S-4 exhibited the strongest inhibitory effect on the Wnt4 protein, as evidenced by the lowest binding energy score of -6782 kcal/mol. Molecular dynamic simulation trajectories revealed that the binding of C29H46N7O18P3S-4 significantly altered the structural dynamics and stability of the Wnt4 protein. These alterations in protein trajectories may have implications for the molecular function of Wnt4 and its associated pathways. Overall, our findings shed light on the inhibitory impact of P. gingivalis-produced metabolites on the Wnt4 protein. Further in vitro, in vivo, and clinical studies are necessary to validate and expand upon our findings.
Keywords: Porphyromonas gingivalis; Wnt4; dental pulp stem cell; docking; endodontic pulpitis; molecular simulation.