PD-1 Suppresses the Osteogenic and Odontogenic Differentiation of Stem Cells From Dental Apical Papilla via Targeting SHP2/NF-κB axis

Abstract BackgroundStem cells from the apical papilla (SCAPs) are important for tooth root development and regeneration of root dentin. Here, we examined the expression of programmed cell death protein-1 (PD-1) in SCAPs and investigated the effect of PD-1 on odontogenic and osteogenic differentiation and the relationship between PD-1 and cell differentiation and SHP2/NF-κB signals.MethodsSCAPs were obtained culture in the related medium. The proliferation ability was evaluated by cell counting kit 8 and 5‐ethynyl‐20‐deoxyuridine (EdU) assay. Alkaline phosphatase (ALP) activity assay, ALP staining, western blot, real-time RT-PCR, Alizarin Red S staining, and immunofluorescence staining were performed to explore the osteo/odontogenic potential and the involvement of SHP2/NF-κB pathways. Besides, we transplanted SCAPs component into mouse calvaria defects to evaluate osteogenesis in vivo. ResultsWe found that human SCAPs expressed PD-1 for the first time. PD-1 knockdown enhanced the osteo/odontogenic differentiation of SCAPs by suppressing SHP2 pathway and activating NF-κB pathway. Overexpression of PD-1 inhibited the osteogenesis and odontogenesis of SCAPs via activation of SHP2 signal and inhibition of NF-κB pathway. ConclusionPD-1 activated SHP2 signal to block NF-κB signal and then played a vital role in osteo/odontogenic differentiation of SCAPs.