The Role of SIRT1 on Angiogenic and Odontogenic Potential in Human Dental Pulp Cells

Introduction: Although several biological roles of SIRT1 have been reported, the expression and role of SIRT1 in human dental pulp cells (HDPCs) remain unknown. To identify the role of SIRT1 in HDPCS, we measured SIRT1 messenger RNA and protein levels during the odontoblastic differentiation of HDPCs. Additionally, we investigated the effects of SIRT1 overexpression and knockdown on the differentiation of HDPCs. Methods: The expression of markers for odontoblastic differentiation and angiogenesis was analyzed by alizarin red staining, reverse-transcriptase polymerase chain reaction, and Western blot analysis. Results: A transient increase in SIRT1 gene expression occurred in early odontogenesis, which peaked at 1 day and decreased thereafter. SIRT1 induction by resveratrol and by infection with adenovirus-SIRT1 (Ad-SIRT1), a SIRT1-expressing adenoviral vector, increased mineralization nodules and up-regulated messenger RNA expression of odontoblastic markers (ie, alkaline phosphatase, osteocalcin, dentin matrix protein-1, and dentin sialophosphoprotein) as well as angiogenic markers (ie, vascular endothelial growth factor, endothelial cell adhesion molecules such as vascular endothelial cadherin and platelet endothelial cell adhesion molecule 1, and fibroblast growth factor-2). In contrast, the inhibition of SIRT1 expression by sirtinol and SIRT1 small interfering RNAs decreased odontoblastic differentiation and down-regulated angiogenic factors. Conclusions: SIRT1 gene activation may provide therapeutic effects in pulp regeneration and dentin tissue engineering. (J Endod 2012;38:899-906)