title: LPS promote the odontoblastic differentiation of human dental pulp stem cells via MAPK signaling pathway.
abstract: Human dental pulp stem cells (hDPSCs) show significant potential for exploitation in novel regeneration strategies, although lack of understanding of their responses to bacterial challenge constrains their application. The present study aimed to investigate whether lipopolysaccharide (LPS), the major pathogenic factor of Gram-negative bacteria, regulates the differentiation of hDPSCs and which intracellular signaling pathways may be involved. LPS treatment significantly promoted the differentiation of hDPSCs demonstrable by increased mineralized nodule formation and mRNA expression of several odontoblastic markers in a dose-dependent manner. While inhibition of TLR4, p38, and ERK signaling markedly antagonized LPS-mediated differentiation of hDPSCs. The inhibition of JNK and NF-κB signaling had no detectable effect on LPS activation of hDPSCs. LPS stimulation resulted in phosphorylation of NF-κB p65, IκB-α, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) in DPSCs in a time-dependent manner, which was markedly suppressed by their specific inhibitors, respectively. Data demonstrated that LPS promoted odontoblastic differentiation of hDPSCs via TLR4, ERK, and P38 MAPK signaling pathways, but not NF-κB signaling.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Wenxi
authors.initials: W
authors.lastname: He
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Luo
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zeyuan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Smith
authors.forename: Paul R
authors.initials: PR
authors.lastname: Cooper
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D003782:Dental Pulp / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4