Caffeic Acid Phenethyl Ester (CAPE) Induces VEGF Expression and Production in Rat Odontoblastic Cells.

Hitomi Kuramoto,Hiromichi Yumoto,Daisuke Takegawa,Takashi Matsuo,Yuki Hosokawa,Kouji Hirao,Ayako Washio,Tadashi Nakanishi,Chiaki Kitamura

doi:10.1155/2019/5390720

Abstract

Caffeic acid phenethyl ester (CAPE), the main component of propolis, has various biological activities including anti-inflammatory effect and wound healing promotion. Odontoblasts located in the outermost layer of dental pulp play crucial roles such as production of growth factors and formation of hard tissue termed reparative dentin in host defense against dental caries. In this study, we investigated the effects of CAPE on the upregulation of vascular endothelial growth factor (VEGF) and calcification activities of odontoblasts, leading to development of novel therapy for dental pulp inflammation caused by dental caries. CAPE significantly induced mRNA expression and production of VEGF in rat clonal odontoblast-like KN-3 cells cultured in normal medium or osteogenic induction medium. CAPE treatment enhanced nuclear factor-kappa B (NF-κB) transcription factor activation, and furthermore, the specific inhibitor of NF-κB significantly reduced VEGF production. The expression of VEGF receptor- (VEGFR-) 2, not VEGFR-1, was up regulated in KN-3 cells treated with CAPE. In addition, VEGF significantly increased mineralization activity in KN-3 cells. These findings suggest that CAPE might be useful as a novel biological material for the dental pulp conservative therapy.

Highlights

Dental caries first occurs on the enamel, the hard outer layer of teeth, and it progresses to dentin, the deep part of the teeth
We first confirmed whether KN-3 cells express the odontoblastic cell markers using RT-PCR and immunoblotting analysis. e gene expression of dentin matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP), encoding the protein of DSP, in KN-3 cells was detected (Figure 1(a))
Cytotoxicity of Caffeic Acid, Caffeic acid phenethyl ester (CAPE), and EGCG on KN-3 Cells. e cytotoxicity of caffeic acid, CAPE, and EGCG on KN-3 cells was investigated by microscopic observation of cell morphology and Lactate Dehydrogenase (LDH) cytotoxicity assay. e specific morphologic change of KN-3 cells by caffeic acid, CAPE, and EGCG was not observed compared to the control (Figures 2(a)–2(d))

Summary

Introduction

Dental caries first occurs on the enamel, the hard outer layer of teeth, and it progresses to dentin, the deep part of the teeth. Dental pulp tissues surrounded by dentin play functional roles in host defense against dental caries-related pathogens. As the tooth defect by dental caries approaches the dental pulp, the patient feels pain with cold and/or hot stimuli and pulpitis becomes apparent. With further progression of dental caries, pulpitis becomes irreversible and severe, and dental pulp removal therapy, called pulpectomy, is performed [1]. Nonvital teeth without dental pulp tissues after pulpectomy have worse prognosis than vital teeth [2]. Erefore, to maintain dental pulp tissues is very important for the longevity of tooth. Erefore, the development of a more ideal dental pulp protective agent that promotes the formation of physiological dentin is expected. In order to develop a novel dental pulp conservative therapy, it is important to elucidate the detailed pathogenesis of pulpitis

Methods

Results

Conclusion