Proinflammatory effects of factor Xa on human dental pulp cells
Kento Nakanishi1, Naoto Kamio1, Takahiro Watanabe1
1Department of Endodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, 271-8587, Japan.
Journal of Oral Biosciences
|November 22, 2025
Summary
Factor Xa (FXa) triggers inflammation in human dental pulp cells by activating protease-activated receptor-2 (PAR-2) and STAT3 signaling, leading to increased COX-2 and prostaglandin E2. This pathway is crucial for understanding pulp inflammation.
Area of Science:
- Biochemistry
- Cell Biology
- Immunology
Background:
- Dental pulp inflammation can cause irreversible tooth damage.
- Factor Xa (FXa), a coagulation factor, is implicated as an inflammatory mediator.
- Protease-activated receptor-2 (PAR-2) signaling is a key pathway in inflammatory responses.
Purpose of the Study:
- To investigate the role of FXa in inducing inflammatory responses in human dental pulp cells (HDPCs).
- To assess the involvement of PAR-2 and STAT3 signaling in FXa-mediated inflammation.
- To evaluate the impact of FXa on COX-2 expression and prostaglandin E2 (PGE2) production.
Main Methods:
- HDPCs were treated with FXa in a time- and concentration-dependent manner.
- COX-2 expression and PGE2 production were measured using RT-PCR, Western blotting, and ELISA.
- PAR-2 localization, STAT3 phosphorylation, and inhibitor effects (AZ3451, rivaroxaban) were analyzed.
Main Results:
- FXa significantly increased COX-2 expression and PGE2 production in HDPCs.
- PAR-2 was localized in inflamed human dental pulp tissues.
- FXa induced STAT3 phosphorylation, and inhibition of PAR-2, FXa, or STAT3 suppressed COX-2 expression.
Conclusions:
- FXa induces COX-2 expression and PGE2 production in HDPCs through PAR-2 and STAT3 signaling.
- This mechanism contributes to pulp inflammation.
- Findings may inform novel therapeutic strategies for preserving dental pulp health.
