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Porphyromonas gingivalis as a Model Organism for Assessing Interaction of Anaerobic Bacteria with Host Cells
Published on: December 17, 2015
Specific microRNA Signature Kinetics in Porphyromonas gingivalis-Induced Periodontitis
Chairmandurai Aravindraja1, Krishna Mukesh Vekariya1, Ruben Botello-Escalante1
1Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
Abstract:
Porphyromonas gingivalis is one of the major bacteria constituting the subgingival pathogenic polymicrobial milieu during periodontitis. Our objective is to determine the global microRNA (miRNA, miR) expression kinetics in 8- and 16-weeks duration of P. gingivalis infection in C57BL/6J mice and to identify the miRNA signatures at specific time-points in mice. We evaluated differential expression (DE) miRNAs in mandibles (n = 10) using high-throughput NanoString nCounter® miRNA expression panels. The bacterial colonization, alveolar bone resorption (ABR), serum immunoglobulin G (IgG) antibodies, and bacterial dissemination were confirmed. In addition, all the infected mice showed bacterial colonization on the gingival surface, significant increases in ABR (p < 0.0001), and specific IgG antibody responses (p < 0.05-0.001). The miRNA profiling showed 26 upregulated miRNAs (e.g., miR-804, miR-690) and 14 downregulated miRNAs (e.g., miR-1902, miR-1937a) during an 8-weeks infection, whereas 7 upregulated miRNAs (e.g., miR-145, miR-195) and one downregulated miR-302b were identified during a 16-weeks infection. Both miR-103 and miR-30d were commonly upregulated at both time-points, and all the DE miRNAs were unique to the specific time-points. However, miR-31, miR-125b, miR-15a, and miR-195 observed in P. gingivalis-infected mouse mandibles were also identified in the gingival tissues of periodontitis patients. None of the previously identified miRNAs reported in in vitro studies using cell lines (periodontal ligament cells, gingival epithelial cells, human leukemia monocytic cell line (THP-1), and B cells) exposed to P. gingivalis lipopolysaccharide were observed in the in vivo study. Most of the pathways (endocytosis, bacterial invasion, and FcR-mediated phagocytosis) targeted by the DE miRNAs were linked with bacterial pathogen recognition and clearance. Further, eighteen miRNAs were closely associated with the bacterial invasion of epithelial cells. This study highlights the altered expression of miRNA in gingiva, and their expression depends on the time-points of infection. This is the first in vivo study that identified specific signature miRNAs (miR-103 and miR-30d) in P. gingivalis invasion of epithelial cells, establishes a link between miRNA and development of periodontitis and helping to better understand the pathobiology of periodontitis.
Insights
This study reveals specific microRNA (miRNA) signatures in mice infected with Porphyromonas gingivalis, linking these molecular changes to periodontitis development and progression over time.
Area of Science:
- Microbiology and Immunology
- Molecular Biology
- Periodontal Disease Research
Background:
- Porphyromonas gingivalis is a key pathogen in periodontitis, a chronic inflammatory gum disease.
- Understanding the host's molecular response, particularly microRNA (miRNA) expression, is crucial for elucidating disease mechanisms.
- Previous studies on miRNA in periodontitis have primarily focused on in vitro models.
Purpose of the Study:
- To investigate the dynamic changes in global miRNA expression in mouse mandibles during Porphyromonas gingivalis infection at 8 and 16 weeks.
- To identify specific miRNA signatures associated with P. gingivalis infection at different time points.
- To correlate in vivo findings with previously reported in vitro miRNA data and identify potential diagnostic or therapeutic targets.
Main Methods:
- High-throughput NanoString nCounter miRNA expression profiling was performed on mandibular tissues from C57BL/6J mice infected with P. gingivalis.
- Bacterial colonization, alveolar bone resorption (ABR), serum IgG antibody levels, and bacterial dissemination were assessed to confirm infection and disease progression.
- Differential expression analysis was used to identify upregulated and downregulated miRNAs at 8 and 16 weeks post-infection.
Main Results:
- P. gingivalis infection led to confirmed bacterial colonization, significant alveolar bone resorption, and specific IgG antibody responses.
- At 8 weeks, 26 miRNAs were upregulated and 14 downregulated; at 16 weeks, 7 miRNAs were upregulated and 1 downregulated.
- miR-103 and miR-30d were consistently upregulated at both time points, and some identified miRNAs (miR-31, miR-125b, miR-15a, miR-195) were also found in human periodontitis tissues.
- Pathways targeted by differentially expressed miRNAs were primarily related to bacterial recognition, invasion, and clearance, with 18 miRNAs linked to bacterial invasion of epithelial cells.
Conclusions:
- This in vivo study demonstrates distinct miRNA expression profiles that change over the course of P. gingivalis infection.
- Specific signature miRNAs, including miR-103 and miR-30d, are identified in the context of P. gingivalis-induced epithelial cell invasion.
- The findings establish a novel link between miRNA dysregulation and periodontitis pathogenesis, offering potential biomarkers and therapeutic avenues.
