Localization of senescent cells under cavity preparations in rats and restoration of reparative dentin formation by senolytics.

Reparative dentin formed by dental cavity preparation (DCP) is frequently used in clinical operations and plays a pivotal role in pulp protection. Recent reports have shown that senescent cells induced by various stressors aggravate many diseases. They can be treated using senolytics, which are drugs that selectively eliminate senescent cells. However, the association between DCP, senescent cells, and senolytics remains unclear. In this study, we established a rat model of DCP and analyzed the spatiotemporal localization of senescent cells in the pulp. The results showed that p21- and p16-positive senescent cells appeared mostly around the pulp horn (PH) under DCP. Furthermore, administration of senolytics (dasatinib and quercetin) successfully eliminated these senescent cells, thereby restoring the volume of reparative dentin formation. These data indicate that senescent cells induced by DCP may hamper the formation of reparative dentin. Senescent cells may be targets for the development of new restorative dentistry therapies.