Specific microRNA Signature Kinetics in <i>Porphyromonas gingivalis</i>-Induced Periodontitis
<i>Porphyromonas gingivalis</i> 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 <i>P. gingivalis</i&g...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2327 |
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| author | Chairmandurai Aravindraja Krishna Mukesh Vekariya Ruben Botello-Escalante Shaik O. Rahaman Edward K. L. Chan Lakshmyya Kesavalu |
| author_facet | Chairmandurai Aravindraja Krishna Mukesh Vekariya Ruben Botello-Escalante Shaik O. Rahaman Edward K. L. Chan Lakshmyya Kesavalu |
| author_sort | Chairmandurai Aravindraja |
| collection | DOAJ |
| description | <i>Porphyromonas gingivalis</i> 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 <i>P. gingivalis</i> 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 (<i>n</i> = 10) using high-throughput NanoString nCounter<sup>®</sup> 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 (<i>p</i> < 0.0001), and specific IgG antibody responses (<i>p</i> < 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 <i>P. gingivalis</i>-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 <i>P. gingivalis</i> 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 <i>P. gingivalis</i> invasion of epithelial cells, establishes a link between miRNA and development of periodontitis and helping to better understand the pathobiology of periodontitis. |
| first_indexed | 2024-03-11T09:42:16Z |
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| id | doaj.art-d86619bb1b7d4a80bda8ae64cd1bf55a |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:42:16Z |
| publishDate | 2023-01-01 |
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| spelling | doaj.art-d86619bb1b7d4a80bda8ae64cd1bf55a2023-11-16T16:55:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243232710.3390/ijms24032327Specific microRNA Signature Kinetics in <i>Porphyromonas gingivalis</i>-Induced PeriodontitisChairmandurai Aravindraja0Krishna Mukesh Vekariya1Ruben Botello-Escalante2Shaik O. Rahaman3Edward K. L. Chan4Lakshmyya Kesavalu5Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610, USADepartment of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610, USADepartment of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610, USADepartment of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USADepartment of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610, USADepartment of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA<i>Porphyromonas gingivalis</i> 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 <i>P. gingivalis</i> 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 (<i>n</i> = 10) using high-throughput NanoString nCounter<sup>®</sup> 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 (<i>p</i> < 0.0001), and specific IgG antibody responses (<i>p</i> < 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 <i>P. gingivalis</i>-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 <i>P. gingivalis</i> 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 <i>P. gingivalis</i> invasion of epithelial cells, establishes a link between miRNA and development of periodontitis and helping to better understand the pathobiology of periodontitis.https://www.mdpi.com/1422-0067/24/3/2327periodontal disease<i>Porphyromonas gingivalis</i>experimental periodontitismiRNAsnanoString analysisdifferential expression miRNAs |
| spellingShingle | Chairmandurai Aravindraja Krishna Mukesh Vekariya Ruben Botello-Escalante Shaik O. Rahaman Edward K. L. Chan Lakshmyya Kesavalu Specific microRNA Signature Kinetics in <i>Porphyromonas gingivalis</i>-Induced Periodontitis International Journal of Molecular Sciences periodontal disease <i>Porphyromonas gingivalis</i> experimental periodontitis miRNAs nanoString analysis differential expression miRNAs |
| title | Specific microRNA Signature Kinetics in <i>Porphyromonas gingivalis</i>-Induced Periodontitis |
| title_full | Specific microRNA Signature Kinetics in <i>Porphyromonas gingivalis</i>-Induced Periodontitis |
| title_fullStr | Specific microRNA Signature Kinetics in <i>Porphyromonas gingivalis</i>-Induced Periodontitis |
| title_full_unstemmed | Specific microRNA Signature Kinetics in <i>Porphyromonas gingivalis</i>-Induced Periodontitis |
| title_short | Specific microRNA Signature Kinetics in <i>Porphyromonas gingivalis</i>-Induced Periodontitis |
| title_sort | specific microrna signature kinetics in i porphyromonas gingivalis i induced periodontitis |
| topic | periodontal disease <i>Porphyromonas gingivalis</i> experimental periodontitis miRNAs nanoString analysis differential expression miRNAs |
| url | https://www.mdpi.com/1422-0067/24/3/2327 |
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