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Surface‑reaction‑type prereacted glass-ionomer (S‑PRG) fillers exhibit bioactive properties by the release of multiple ions. This study examined whether a novel endodontic sealer containing S‑PRG fillers (PRG+) has the capacity to induce osteoblast differentiation. Kusa‑A1 osteoblastic cells were cultured with extracts of PRG+, PRG- (an experimental sealer containing S‑PRG‑free silica fillers), AH Plus (an epoxy-resin‑based sealer), and Canals N (a zinc-oxide noneugenol sealer). Cell viability and mineralized nodule formation were determined using WST‑8 assay and Alizarin red staining, respectively. Osteoblastic-marker expression was analyzed with RT‑qPCR and immunofluorescence. Phosphorylation of extracellular signal‑regulated kinase (ERK) and p38 mitogen‑activated protein kinase (MAPK) was determined with Western blotting. Extracts of freshly mixed PRG+, PRG-, and AH Plus significantly decreased cell growth, but extracts of the set samples were not significantly cytotoxic. Set PRG+ significantly upregulated mRNAs for alkaline phosphatase and bone sialoprotein (IBSP) compared to set PRG-, and upregulation was blocked by NPS2143, a calcium‑sensing receptor antagonist. Set PRG+ significantly accelerated IBSP expression, mineralized nodule formation, and enhanced the phosphorylation of ERK and p38 compared with set PRG-. In conclusion, PRG+ induced the differentiation and mineralization of Kusa‑A1 cells via the calcium-sensing receptor-induced activation of ERK and p38 MAPK.

A Novel Bioactive Endodontic Sealer Containing Surface-Reaction-Type Prereacted Glass-Ionomer Filler Induces Osteoblast Differentiation