Caffeic Acid Phenethyl Ester Enhances Bone Repair-related Factors in MC3T3-E1 Cells

Apical periodontitis is an inflammatory disease caused by bacterial infection in the root canal that spreads to the apical periodontal tissues, resulting in bone resorption around the root apex as the disease progresses. Vascular endothelial growth factor (VEGF), a growth factor involved in angiogenesis, plays an important role in bone remodeling. We reported that caffeic acid phenethyl ester (CAPE), a bioactive substance of propolis, induces VEGF in odontoblast-like cells and dental pulp cells. However, the effects of CAPE on bone tissues remain unclear. This study was aimed to investigate the effects of CAPE on MC3T3-E1 cells, mice preosteoblast line. As a result, CAPE up-regulated the production of VEGF and induced the phosphorylation of extracellular signal-regulated kinases (ERK), p38 mitogen-activated protein kinase (MAPK), and stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) in MC3T3-E1 cells. Furthermore, CAPE increased the expression of factors involved in osteoblast differentiation, runt-related transcription factor 2 (Runx2), Osterix, and Wnt5a/b in MC3T3-E1 cells. In this study, we show that CAPE could induce bone repair-related factors in MC3T3-E1 cells.