Bone Abstracts

Smurf1 is an E3 ubiquitin ligase for Smad1/5, Runx2 and MEKK2 and plays a role as a negative regulator for osteoblast differentiation and bone formation. However, the role of Smurf1 in odontoblast differentiation has not been elucidated. Previously, we reported that histone deacetylase inhibitors (HDACi) enhance odontoblast differentiation through the upregulation of Nfic expression. In this study, we investigated the regulatory effect of HDACi on Smurf1 expression and the role of Smurf1 in odontoblast differentiation. The effects of HDACi (SAHA, Trichostatin A) on the Smurf1 expression and odontoblast differentiation were observed in MDPC23 cells, a murine pre-odontoblast cell line. HDACi increased Nfic expression while decreasing Smurf1 expression. Overexpression of Nfic decreased Smurf1 expression whereas Nfic knockdown increased Smurf1 expression. Treatment with HDACi or overexpression of Nfic reduced the levels of RNA polymerase II binding, acetyl-H3 and methyl-H3K4 in the DNA region spanning the Smurf1 promoter and transcription start site, suggesting that HDACi/Nfic downregulate Smurf1 transcription. Smurf1 overexpression decreased the expression levels of odontoblast differentiation marker genes such as DMP1, Nestin and DSPP and matrix mineralization. Similar to HDACi treatment, Smurf1 knockdown enhanced the expression levels of odontoblast differentiation marker genes. These results suggest that HDACi downregulate Smurf1 expression through the induction of Nfic expression and that reduction in Smurf1 level contribute to HDACi-induced odontoblast differentiation.