Piperine induces osteoblast differentiation through AMPK-dependent Runx2 expression.

Piperine is an alkaloid responsible for the pungency of black pepper and long pepper. It is reported to have various biological actions such as anti-oxidative and anti-inflammatory, and aids cancer prevention. Antioxidants have been shown to promote osteoblast differentiation. However, osteoblast differentiation by piperine has not yet been elucidated. Piperine-induced expression of the osteogenic genes such as distal-less homeobox 5 (Dlx5), inhibitor of DNA binding-1 (Id1), and runt-related transcription factor 2 (Runx2) was investigated using RT-PCR. In addition, alkaline phosphatase (ALP) activity and mineralization was found to be increased by piperine treatment. Finally, we confirmed that piperine induced phosphorylation of AMPK in MC3T3-E1 cells. Taken together, these results demonstrate that piperine enhance osteoblast differentiation through AMPK phosphorylation in MC3T3-E1 cells.