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

• Published in: Inflammation Vol. 36; no. 6; pp. 1393 - 1402
• Main Authors: Wang, Jia, Dai, Jiewen, Liu, Bin, Gu, Shensheng, Cheng, Lan, Liang, Jingping
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2013
• Subjects: Adolescent; Adult; Apexification; beta Catenin - metabolism; Biomedical and Life Sciences; Biomedicine; Cyclin D1 - genetics; Dental Papilla - cytology; Dental Papilla - metabolism; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Humans; Immunology; Interleukin-1beta - biosynthesis; Interleukin-1beta - genetics; Internal Medicine; Lipopolysaccharides; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Pathology; Pharmacology/Toxicology; Porphyromonas gingivalis - metabolism; Proto-Oncogene Proteins c-myc - genetics; Rheumatology; RNA, Messenger - biosynthesis; Stem Cells; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Wnt Proteins - metabolism; Wnt Signaling Pathway; Young Adult; GSK-3β; Wnt/β-catenin signalling pathway; p38 MAPK; .; LPS
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-013-9679-y

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.