Acetylsalicylic Acid Treatment and Suppressive Regulation of AKT Accelerate Odontogenic Differentiation of Stem Cells from the Apical Papilla

Stem cells isolated from the root apical papilla of human teeth (stem cells from the apical papilla [SCAPs]) are capable of forming tooth root dentin and are a feasible source for bioengineered tooth root regeneration. In this study, we examined the effect of acetylsalicylic acid (ASA) on odontogenic differentiation of SCAPs in vitro and in vivo. SCAPs were cultured under odontogenic conditions supplemented with or without ASA. ASA-treated SCAPs were also subcutaneously transplanted into immunocompromised mice. ASA accelerates in vitro and in vivo odontogenic differentiation of SCAPs associated with down-regulation of runt-related nuclear factor 2 and up-regulation of specificity protein 7, nuclear factor I C, and dentin phosphoprotein. ASA up-regulated the phosphorylation of AKT in the odontogenic SCAPs. Of interest, pretreatments with phosphoinositide 3-kinase inhibitor LY294402 and small interfering RNA for AKT promoted ASA-induced in vitro and in vivo odontogenic differentiation of SCAPs. LY294402 and small interfering RNA for AKT also suppressed the ASA-induced expression of runt-related nuclear factor 2 and enhanced ASA-induced expression of specificity protein 7, nuclear factor I C, and dentin phosphoprotein in SCAPs. These findings suggest that a combination of ASA treatment and suppressive regulation of the phosphoinositide 3-kinase–AKT signaling pathway is a novel approach for SCAP-based tooth root regeneration. •Acetylsalicylic acid promotes the in vitro and in vivo odontogenic differentiation of stem cells from the apical papilla (SCAPs).•Acetylsalicylic acid suppresses the phosphoinositide 3-kinase–AKT pathway in SCAPs during the odontogenic differentiation.•Acetylsalicylic acid could provide a novel adjuvant in regenerative endodontics.