Low Concentration of Etoposide Induces Enhanced Osteogenesis in MG63 Cells via Pin1 Activation

抄録

This study aimed to examine whether a low concentration of etoposide can accelerate osteogenesis via the activation of peptidyl-prolyl isomerase Pin1 in human MG63 cells using a genetic knockdown approach. MG63 cells treated with 0.1 μM etoposide for 24 h showed neither reduction in cell viability nor induction of cellular senescence; however, there was a significant increase in the percentage of nuclear staining with γH2AX as compared with that in untreated control cells, indicating that 0.1 μM etoposide induces weak DNA damage response (DDR) in the cells. Treatment with 0.1 μM etoposide accelerates osteogenesis in osteogenic induction medium (OIM)-cultured MG63 cells, demonstrating increased expression of Runx2 and Osterix and intense alkaline phosphatase (ALP) staining, as compared with cells treated without etoposide. In addition to those osteogenic markers, Pin1 expression was upregulated in the etoposide-treated cells, suggesting that the weak DDR may provide an interaction between Pin1 activation and osteogenic markers. The RNA interference-mediated silencing of Pin1 suppressed the expression of osteogenic markers and ALP staining in the OIM-cultured cells pretreated with 0.1 μM etoposide. Based on these findings, we suggest that a low concentration of etoposide induces mild DDR to activate Pin1, eventually promoting OIM-induced osteogenesis in the MG63 cells.