2018 Volume 60 Issue 1 Pages 13-25
Berberine, which is an extract of Coptis Rhizome, has been used in Chinese Medicine for the prevention and treatment of oral diseases. Recent studies have suggested that berberine is useful for inducing bone regeneration. It is known that undifferentiated mesenchymal stem cells in the periodontal ligament play an important role in the regeneration of periodontal tissue. However, little is known about the effects of berberine on the periodontal ligament cells. In this study, the effects of berberine on human periodontal ligament-derived fibroblasts (hPDL cells) and immortalized mouse cementoblasts were analyzed, and it was revealed that berberine induced proliferation of these cells. On the other hand, berberine significantly inhibited the gene expression and enzyme activity of alkaline phosphatase (ALP). No significant effect of berberine was seen on the gene expression of osteocalcin or bone sialoprotein. Berberine induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK 1/2) in hPDL cells. However, SB203580 (p38 MAPK inhibitor) and PD98059 (ERK1/2 inhibitor), which are inhibitors of these two kinases, respectively, showed no significant inhibitory effect on the enhancement of cell proliferation mediated by berberine. In addition, pretreatment of the cells with PD98059 abrogated the suppressive effect of berberine on the gene expression and enzyme activity of ALP, suggesting that berberine suppresses ALP gene expression and enzyme activity via the ERK1/2 pathway. These results suggest that berberine promotes mesenchymal cell proliferation while keeping their differentiation level into periodontal ligament cells at a low level.