IFN-I 3 regulates human dental pulp stem cells behavior via NF-I B and MAPK signaling

Abstract

During caries, dental pulp expresses a range of pro-inflammatory cytokines in response to the infectious challenge. Interferon gamma (IFN-I 3) is a dimerized soluble cytokine, which is critical for immune responses. Previous study has demonstrated that IFN-I 3 at relative high concentration (100 ng/mL) treatment improved the impaired dentinogenic and immunosuppressive regulatory functions of disease-derived dental pulp stem cells (DPSCs). However, little is known about the regulatory effects of IFN-I 3 at relative low concentration on healthy DPSC behavior (including proliferation, migration, and multiple-potential differentiation). Here we demonstrate that IFN-I 3 at relatively low concentrations (0.5 ng/mL) promoted the proliferation and migration of DPSCs, but abrogated odonto/osteogenic differentiation. Additionally, we identified that NF-I B and MAPK signaling pathways are both involved in the process of IFN-I 3-regulated odonto/osteogenic differentiation of DPSCs. DPSCs treated with IFN-I 3 and supplemented with pyrrolidine dithiocarbamate (PDTC, an NF-I B inhibitor) or SB203580 (a MAPK inhibitor) showed significantly improved potential for odonto/osteogenic differentiation of DPSCs both in vivo and in vitro. These data provide important insight into the regulatory effects of IFN-I 3 on the biological behavior of DPSCs and indicate a promising therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment.