Astragaloside IV (AS-IV), a natural herbal compound from Astragalus membranaceus, has inhibitory effects on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, and RANKL signal helps to regulate odontoblast differentiation. However, whether and how AS-IV affects odontoblastic differentiation remains unclear.Lipopolysaccharide (LPS)-stimulated MDPC-23 cells and rat pulpitis were treated with AS-IV, cell viability, and LDH leakage was analyzed by CCK-8 assay and LDH Leakage assay. The production of TNF-α and IL-6 was determined by ELISA and qRT-PCR assay. The expression of alkaline phosphatase (ALP) was detected using an ALP assay kit, and the expression of dentin sialophos-phoprotein (DSPP), dentin matrix protein-1 (DMP1), basic fibroblast growth factor (FGF2), and phosphorylated extracellular signal-regulated kinase (p-ERK) was determined by western blot.AS-IV dose dependently increased in cell viability and decreased the overproduction of TNF-α and IL-6 in LPS-stimulated MDPC-23 cells. AS-IV also counteracted LPS-induced downregulation of ALP, DSPP, and DMP1 in MDPC-23 cells. Furthermore, AS-IV significantly decreased the expression of FGF2 and p-ERK in LPS-stimulated MDPC-23 cells. More important, the addition of FGF2 partly neutralized AS-IV-mediated inhibition of FGF2/ERK signaling, abolished AS-IV-induced reduction of TNF-α and IL-6, and counteracted AS-IV-induced upregulation of DSPP and DMP-1 in these cells. Meanwhile, AS-IV inhibited the excessive production of TNF-α and IL-6, suppressed the downregulation of DSPP and DMP1, and disturbed the up-regulation of FGF2 and p-ERK in the pulp tissues of rat pulpitis model.AS-IV exerted anti-inflammatory and pro-differentiation effects in LPS-stimulated MDPC-23 cells and rat pulpitis via inhibiting the FGF2/ERK signaling pathway.
