Overexpressed Sirt1 in MSCs Promotes Dentin Formation in Bmi1-Deficient 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 Sirt1 TG mice and dramatically reduced in the Bmi1 –/– mice versus the WT littermates at 4 wk of age. However, the areas of predentin and the percentage of TUNEL-positive apoptotic cells were significantly reduced in the Sirt1 TG mice but dramatically increased in the Bmi1 −/− mice as compared with the WT littermates.

All these parameters were rescued in the Sirt1 TG Bmi1 −/− mice versus the Bmi1 −/− mice. Finally, by using dental papilla mesenchymal cells, we found that the overexpression of Sirt1 rescued the reduced cell proliferation and differentiation and increased the cell apoptosis caused by Bmi1 deficiency, which was associated with increased p53 deacetylation. Therefore, this study indicates that Sirt1 is a potential therapeutic target for promoting dentin formation in an anabolic approach to the treatment of dental developmental defects.