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

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.

Bioinductive and anti-inflammatory properties of Propolis and Biodentine on SHED

“…Simultaneously, VEGF increased the mineralisation activity in KN-3 cells. These findings suggested that CAPE might be useful as a novel biological material for dental pulp therapy ( Kuramoto et al, 2019 ). Therefore, propolis and its active components are most likely responsible for osteogenic/odontogenic differentiation of SHED.…”

Caffeic Acid Phenethyl Ester Induces Vascular Endothelial Growth Factor Production and Inhibits CXCL10 Production in Human Dental Pulp Cells

“…The findings of their previous reports except simultaneous stimulation are similar to the present study. Recently, we first demonstrated upregulated production of VEGF by CAPE in odontoblastic KN-3 cells [ 19 ]. In this study, VEGF production by CAPE was induced regardless of the presence of Pam3CSK4 or TNF-α on HDPCs.…”

“…CAPE was reported to have an inhibitory effect on tumor necrosis factor (TNF)-induced CXCL10 expression in mouse intestinal epithelial cells [ 18 ]. We have already shown that CAPE can induce VEGF, and moreover, VEGF can enhance mineralization activity in the rat odontoblastic cell line (KN-3 cells) established by limiting dilution cloning from dental papilla cells of lower incisors in Wistar rats [ 19 ]. However, the effect of CAPE on HDPCs has not yet been examined.…”

An Overview of the Use of Medicinal Plants in Regenerative Dentistry

“…Pinus massoniana have been studied [40] for inducing odontogenic differentiation, also Astragalus membnaceus [41], curcuma longa [42] [43] [44], Camellia sinensis [45] and Cinnamomum verum [43] [45], Allium sativum have shown an acceleration on the healing process and antibacterial effects [46]. Cafeic acid combined to MTA have shown angiogenic properties and formation of hydroxyapatite, immunosuppressive and odontogenic properties [47] [48] [49], Proanthocyanidins induces odontogenic differentiation and increases the expression of biomineralization and odontogenic differentiation regulators: RUNX2, BMP2, OCN and DSPP [36]…”