Overexpressed Sirt1 in MSCs Promotes Dentin Formation in Bmi1-Deficient Mice:

Sirt1 promotes odontoblastic gene expression in human dental pulp cells, whereas the inhibition of Sirt1 downregulates the expression of those genes. To investigate whether the overexpression of Sirt1 in mesenchymal stem cells (MSCs) driven by Prx1 promoter could rescue the dentin formation defects in Bmi1-deficient (Bmi1−/−) mice, we established the MSCs overexpressing Sirt1 in Bmi1 knockout mice (Sirt1TGBmi1−/−). First, we used Prx1-Cre/ROSAnTnG mice to demonstrate that Prx1 linage cells exist mainly in the pulp horns at 4 wk of age. Second, we found that 4-wk-old Sirt1TG mice had increased tooth volume as compared with wild-type (WT) littermates. The expression level of Sirt1 was significantly higher in dental papilla mesenchymal cells of Sirt1TG mice than WT mice. Furthermore, we demonstrated that the tooth mineralization, dental volume, dentin sialoprotein–immunopositive areas, odontoblastic gene expression, and percentage of proliferating BrdU-positive cells were significantly elevated in the Sirt1T...