The Effects of Mitogen-activated Protein Kinase Signaling Pathways on Lipopolysaccharide-mediated Osteo/Odontogenic Differentiation of Stem Cells from the Apical Papilla

Introduction: Odontogenic differentiation of human stem cells from the apical papilla (SCAPs) is a prerequisite step in the root development of immature permanent teeth. However, little is known about the effects of an inflammatory environment on osteo/odontogenic differentiation of SCAPs. The purpose of this study was to investigate the effects of lipopolysaccharide (LPS) on the proliferation and osteo/odontogenic differentiation of SCAPs and the role of mitogen-activated protein kinase (MAPK) signaling pathways in LPS-mediated osteo/odontogenic differentiation of SCAPs. Methods: SCAPs of human third permanent molars were cultured. Cell viability was analyzed. Alkaline phosphatase activity and mineralization ability were investigated. Gene expression of osteo/odontogenic differentiation and MAPK signaling pathways was evaluated during osteo/odontogenic differentiation of SCAPs. Results: In the 0.1 mu g/mL LPS treated group, cell proliferation, alkaline phosphatase activity, and mineralization of SCAPs were up-regulated. Real-time quantitative polymerase chain reaction revealed that dentin sialophosphoprotein, runt-related transcription factor 2, and bone sialoprotein were increased. However, we did not detect any change of osteocalcin expression. In addition, the expression of p-ERK and p-p38 in SCAPs was enhanced by LPS treatment, whereas the inhibition of ERK and p38 MAPK pathways markedly suppressed the differentiation of LPS-treated SCAPs. Conclusions: Our findings showed that LPS at the appropriate concentration promoted the proliferation and osteo/odontogenic differentiation of SCAPs. ERK and p38 MAPK signaling pathways are involved in LPS-mediated osteo/odontogenic differentiation of SCAPs.