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Porphyromonas gingivalis Lipopolysaccharide Activates Canonical Wnt/β-Catenin and p38 MAPK Signalling in Stem Cells from the Apical Papilla

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Abstract

As dental precursor cells, stem cells from the apical papilla (SCAP) are capable of forming roots and undergoing apexogenesis, which are impaired upon exposure to bacterial infection. Porphyromonas gingivalis is a common Gram-negative bacterium that is involved in pulpal and periapical infection. The purpose of this study was to investigate the effects of P. gingivalis lipopolysaccharide (LPS) on the Wnt/β-catenin and p38 mitogen-activated protein kinase (MAPK) signalling pathways in SCAP. As indicated by the IL-1β and TNF-α mRNA levels, P. gingivalis LPS induced the expression of pro-inflammatory cytokines in a dose-dependent manner. In addition, activation of the p38 MAPK and Wnt/β-catenin pathways was confirmed by the augmentation of phospho-p38 and β-catenin protein expression and increased expression of c-myc and cyclin D1 mRNA. Despite no significant increase in β-catenin mRNA expression, increased phosphorylation of glycogen synthase kinase (GSK)-3β suggested that GSK-3β was responsible for the accumulation of β-catenin in the cytoplasm and translocation to the nucleus. Previous studies have shown that GSK-3β plays a critical role in crosstalk between the Wnt/β-catenin and p38 MAPK pathways. In the present study, we showed that the level of p38 phosphorylation decreased upon pretreatment with a p38 MAPK inhibitor for 1 h before stimulating SCAP with 10 μg/ml P. gingivalis LPS. However, the levels of GSK-3β and β-catenin phosphorylation in the cytoplasm and nucleus were not significantly altered. Our results suggest that the p38 MAPK and canonical Wnt/β-catenin signalling pathways are activated by P. gingivalis LPS in SCAP, but we have no evidence that p38 MAPK is upstream of GSK-3β in the Wnt/β-catenin signalling pathway.

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ACKNOWLEDGMENTS

This work was supported by grant 81271133 from the National Natural Science Foundation of China.

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Authors and Affiliations

  1. Department of Endodontics and Operative Dentistry, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, No. 639, Zhizaoju Road, Shanghai, 200011, People’s Republic of China

    Jia Wang, Bin Liu, Shensheng Gu & Jingping Liang

  2. Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China

    Jia Wang, Jiewen Dai, Bin Liu, Shensheng Gu, Lan Cheng & Jingping Liang

  3. Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China

    Jiewen Dai

  4. Department of Periodontology, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China

    Lan Cheng

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  1. Jia Wang
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Correspondence to Jingping Liang.

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Wang, J., Dai, J., Liu, B. et al. Porphyromonas gingivalis Lipopolysaccharide Activates Canonical Wnt/β-Catenin and p38 MAPK Signalling in Stem Cells from the Apical Papilla. Inflammation 36, 1393–1402 (2013). https://doi.org/10.1007/s10753-013-9679-y

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