Combination of dasatinib and quercetin promotes osteogenic differentiation and stemness maintenance of hPDLSCs via YAP/TAZ.

Abstract

Human periodontal ligament stem cells (hPDLSCs) are candidate seed cells for periodontal tissue regeneration. Enhancing the stemness maintenance and osteogenic differentiation potential of hPDLSCs is conducive to their role in periodontal tissue regeneration. The combination of dasatinib and quercetin, a type of senolytic, has been reported to affect cell senescence. However, whether it can regulate the osteogenic differentiation and stemness maintenance of hPDLSCs, and the related mechanisms, remain unknown. The present study analyzed the optimal concentrations of dasatinib and quercetin in combination for hPDLSCs and found that the combination of dasatinib and quercetin enhanced osteogenic differentiation and promoted the expression of stemness-related markers in hPDLSCs. The expression levels of TAZ and YAP were improved when hPDLSCs were incubated with dasatinib and quercetin. However, the osteogenesis-promoting effects of dasatinib plus quercetin were partly attenuated when TAZ was knocked down, and their effects on stemness-related markers were suppressed when YAP was inhibited. Taken together, the combination of dasatinib and quercetin promotes the osteogenic differentiation and stemness maintenance of hPDLSCs, and YAP/TAZ may be involved in this process. This combination may hold promise for improving hPDLSCs function in periodontal tissue regeneration.