Abstract
Introduction
Prostaglandin E2 (PGE2) exerts biological actions through its transport pathway involving intracellular
synthesis, extracellular transport, and receptor binding. This study aimed to determine
the localization of the components of the PGE2-transporting pathway in human dental pulp and explore the relevance of PGE2 receptors (EP2/EP4) to angiogenesis and dentinogenesis.
Methods
Protein localization of microsomal PGE2 (mPGES)synthase, PGE2 transporters (multidrug resistance-associated protein-4 [MRP4] and prostaglandin
transporter [PGT]), and EP2/EP4 was analyzed using double immunofluorescence staining.
Tooth slices from human third molars were cultured with or without butaprost (EP2
agonist) or rivenprost (EP4 agonist) for 1 week. Morphometric analysis of endothelial
cell filopodia was performed to evaluate angiogenesis, and real-time polymerase chain
reaction was performed to evaluate angiogenesis and odontoblast differentiation markers.
Results
MRP4 and PGT were colocalized with mPGES and EP2/EP4 in odontoblasts and endothelial
cells. Furthermore, MRP4 was colocalized with mPGES and EP4 in human leukocyte antigen-DR-expressing
dendritic cells. In the tooth slice culture, EP2/EP4 agonists induced significant
increases in the number and length of filopodia and mRNA expression of angiogenesis
markers (vascular endothelial growth factor and fibroblast growth factor-2) and odontoblast
differentiation markers (dentin sialophosphoprotein and collagen type 1).
Conclusions
PGE2-producing enzyme (mPGES), transporters (MRP4 and PGT), and PGE2-specific receptors (EP2/EP4) were immunolocalized in various cellular components
of the human dental pulp. EP2/EP4 agonists promoted endothelial cell filopodia generation
and upregulated angiogenesis- and odontoblast differentiation-related genes, suggesting
that PGE2 binding to EP2/EP4 is associated with angiogenic and dentinogenic responses.
Key Words
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Article info
Publication history
Published online: February 07, 2023
Identification
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© 2023 American Association of Endodontists.
