title: IFN-γ regulates human dental pulp stem cells behavior via NF-κB and MAPK signaling.
abstract: During caries, dental pulp expresses a range of pro-inflammatory cytokines in response to the infectious challenge. Interferon gamma (IFN-γ) is a dimerized soluble cytokine, which is critical for immune responses. Previous study has demonstrated that IFN-γ 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-γ at relative low concentration on healthy DPSC behavior (including proliferation, migration, and multiple-potential differentiation). Here we demonstrate that IFN-γ 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-κB and MAPK signaling pathways are both involved in the process of IFN-γ-regulated odonto/osteogenic differentiation of DPSCs. DPSCs treated with IFN-γ and supplemented with pyrrolidine dithiocarbamate (PDTC, an NF-κB 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-γ on the biological behavior of DPSCs and indicate a promising therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry &Endodontics, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.|Shaanxi Key Laboratory of Stomatology, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.
authors.forename: Xinyao
authors.initials: X
authors.lastname: He
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry &Endodontics, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.|Shaanxi Key Laboratory of Stomatology, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry &Endodontics, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.|Department of Stomatology, the Affiliated Hospital of Guizhou Medical University, Guiyang Guizhou, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry &Endodontics, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.|Shaanxi Key Laboratory of Stomatology, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry &Endodontics, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.|Shaanxi Key Laboratory of Stomatology, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry &Endodontics, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.|Shaanxi Key Laboratory of Stomatology, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry &Endodontics, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.|Shaanxi Key Laboratory of Stomatology, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Oral Biology, School of Dentistry, University of Birmingham, B4 6NN, UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Cooper
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry &Endodontics, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.|Shaanxi Key Laboratory of Stomatology, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.
authors.forename: Wenxi
authors.initials: W
authors.lastname: He
mesh_terms: D015415:Biomarkers; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010012:Osteogenesis; D010641:Phenotype; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016328:NF-kappa B; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases