Global Noncoding microRNA Profiling in Mice Infected with Partial Human Mouth Microbes (PAHMM) Using an Ecological Time-Sequential Polybacterial Periodontal Infection (ETSPPI) Model Reveals Sex-Specific Differential microRNA Expression

Aravindraja, Chairmandurai; Kashef, Matteen R.; Vekariya, Krishna Mukesh; Ghanta, Ravi K.; Karanth, Shama D.; Chan, Edward K. L.; Kesavalu, Lakshmyya

doi:10.3390/ijms23095107

Cited by 6 publications

(61 citation statements)

References 67 publications

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“…We previously reported that the oral inoculation of Gram-negative subgingival periodontal bacteria ( P. gingivalis , T. denticola , or T. forsythia ) promotes bacterial colonization on the gingival surface and induces miRNA expression [ 19 , 23 , 25 , 30 , 31 ]. In the present study, new experiments were conducted designed to examine whether Gram-positive S. gordonii , inhabiting the supragingival region can colonize gingival epithelium and induce PD in mice.…”

Section: Resultsmentioning

confidence: 99%

“…The sex-specific DE miRNA reported in the partial human mouth microbes (PAMHH)- ETSPPI model that utilized five different bacteria including S. gordonii (early bacterial colonizer), F. nucleatum (intermediate bacterial colonizer), P. gingivalis, T. denticola and T. forsythia (late bacterial colonizers) using a time sequential infection [ 19 ]. Recently, we reported a polybacterial PD mouse model that induced miRNA expression, but the novelty of studying specific bacterium S. gordonii alone in inducing PD and specific miRNAs DE was not examined.…”

Section: Discussionmentioning

confidence: 99%

“…The inflammatory miRNA (miR-146b) reported in the PD subjects is also upregulated in the 8- and 16-week S. gordonii -infected mice [ 120 ]. Thirty-three miRNAs (e.g., miR-375, 148a, 574-3p, 382, and 181c) DE in the polymicrobial infection [ 19 ] are also expressed in the present S. gordonii monobacterial infection (Female comparison). Twenty-three miRNAs (e.g., miR-200b, 2141, 202-5p, and 1902) DE in the polymicrobial infection [ 19 ] are also expressed in the present S. gordonii monobacterial infection (Male comparison).…”

Section: Discussionmentioning

confidence: 99%

“…MiRNAs are resistant to degradation by ribonucleases and have been shown to be potential biomarkers for disease prediction and diagnosis. Accordingly, an improved understanding of the biogenesis pattern of miRNAs could potentially lead to the development of novel diagnostic biomarkers for polymicrobial infection-driven inflammatory diseases [ 19 ]. S. gordonii increased the expression of miR-4516 and miR-663a in the human oral epithelial cells, modulating validated targets of chemokine-associated pathways [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…The inflammatory miRNAs miR-21 [ 21 ], miR-325-3p [ 22 ], miR-27a, miR-34a [ 23 ], miR-132 [ 24 , 25 ], miR-146a, miR-155 [ 26 , 27 ], miR-126-3p [ 28 , 29 ] miR-200, and mmu-let-7a [ 23 ] have been reported in the initiation and progression of PD. Recently, we characterized alterations in sex-specific microRNA after partial human mouth microbes (PAHMM) in an ecological time-sequential polybacterial periodontal infection (ETSPPI) mouse model and identified seven miRNAs (miR-9, miR-148a, miR-669a, miR-199a-3p, miR-1274a, miR-377, and miR-690) in both sexes that may be implicated in the pathogenesis of PD [ 19 ]. The five miRNAs (miR-195, 31, 125b-5p, 15a, and 423-5p) that were DE during the P. gingivalis monobacterial infection [ 30 ] and the seven miRs (miR-22, 486, 126-3p, 378, 151a-3p, 423-5p, and 221) during T. denticola monobacterial infection were also DE in chronic PD with diabetes [ 25 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

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Streptococcus gordonii Supragingival Bacterium Oral Infection-Induced Periodontitis and Robust miRNA Expression Kinetics

Aravindraja,

Jeepipalli,

Duncan

et al. 2024

IJMS

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Streptococcus gordonii (S. gordonii, Sg) is one of the early colonizing, supragingival commensal bacterium normally associated with oral health in human dental plaque. MicroRNAs (miRNAs) play an important role in the inflammation-mediated pathways and are involved in periodontal disease (PD) pathogenesis. PD is a polymicrobial dysbiotic immune-inflammatory disease initiated by microbes in the gingival sulcus/pockets. The objective of this study is to determine the global miRNA expression kinetics in S. gordonii DL1-infected C57BL/6J mice. All mice were randomly divided into four groups (n = 10 mice/group; 5 males and 5 females). Bacterial infection was performed in mice at 8 weeks and 16 weeks, mice were euthanized, and tissues harvested for analysis. We analyzed differentially expressed (DE) miRNAs in the mandibles of S. gordonii-infected mice. Gingival colonization/infection by S. gordonii and alveolar bone resorption (ABR) was confirmed. All the S. gordonii-infected mice at two specific time points showed bacterial colonization (100%) in the gingival surface, and a significant increase in mandible and maxilla ABR (p < 0.0001). miRNA profiling revealed 191 upregulated miRNAs (miR-375, miR-34b-5p) and 22 downregulated miRNAs (miR-133, miR-1224) in the mandibles of S. gordonii-infected mice at the 8-week mark. Conversely, at 16 weeks post-infection, 10 miRNAs (miR-1902, miR-203) were upregulated and 32 miRNAs (miR-1937c, miR-720) were downregulated. Two miRNAs, miR-210 and miR-423-5p, were commonly upregulated, and miR-2135 and miR-145 were commonly downregulated in both 8- and 16-week-infected mice mandibles. Furthermore, we employed five machine learning (ML) algorithms to assess how the number of miRNA copies correlates with S. gordonii infections in mice. In the ML analyses, miR-22 and miR-30c (8-week), miR-720 and miR-339-5p (16-week), and miR-720, miR-22, and miR-339-5p (combined 8- and 16-week) emerged as the most influential miRNAs.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Streptococcus gordonii Supragingival Bacterium Oral Infection-Induced Periodontitis and Robust miRNA Expression Kinetics

Aravindraja,

Jeepipalli,

Duncan

et al. 2024

IJMS

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The Evaluation of a 5-miRNA Panel in Patients with Periodontitis Disease

Baru,

Pop,

Raduly

et al. 2024

JDR Clinical & Translational Research

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Introduction: Side by side with tooth decay, periodontitis remains one of the most common oral diseases and is increasingly recognized as a serious public health concern worldwide. Objectives: The present study aims at comparing the levels of 5 specific miRNAs (miR-29b-3p, miR-34a-5p, miR-155-5p, miR-181a-5p, and miR-192-5p) in patients with periodontal disease and healthy controls. Methods: The pathogenic mechanism is related to the activation of immune response and significant alteration of coding and noncoding genes, including miRNA. The study includes 50 subjects (17 with periodontal disease and 33 healthy controls) with a mean age of 45.3 y. In both periodontitis patients and healthy controls, a panel of 5 miRNAs (miR-29b-3p, miR-34a-5p, miR-155-5p, miR-181a-5p, and miR-192-5p) is examined by determining their expression levels with quantitative reverse transcription polymerase chain reaction. Results: The periodontitis patients express high levels of all the investigated miRNAs. Receiver operating characteristic curve analysis shows an area under the curve (AUC) of 0.69 to 0.74 for individual transcripts with the highest AUC value observed for miR-192, followed by miR-181a. Conclusions: The study indicates that the 5-miRNA panel can be used as biomarker for periodontitis. In this way, all implantology procedures and treatment options for patients diagnosed with periodontitis can be improved for better long-term results, predictability, and follow-up frequency. Knowledge Transfer Statement: The discovery of a miRNA panel as a potential biomarker for periodontitis offers major opportunities for practical application. Our study can improve diagnostic accuracy; researchers can develop new theories on molecular mechanisms and biomarker discovery.

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Oral Spirochete <em>Treponema denticola </em>Intraoral Infection Reveals Unique miR-133a, miR-486, miR-126-3p, miR-126-5p miRNA Expression Kinetics during Periodontitis

Aravindraja¹,

Jeepipalli²,

Vekariya³

et al. 2023

Preprint

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miRNAs are major regulators of eukaryotic gene expression, host immunity, and play an important role in the inflammation-mediated pathways in periodontal disease (PD) pathogenesis. Expanding our previous observation with the global miRNA profiling using partial human mouth microbes and lack of in vivo studies involving oral spirochete Treponema denticola induced miRNAs, this study was designed to delineate the global miRNA expression kinetics during progression of periodontitis in mice infected with T. denticola by using NanoString nCounter® miRNA panels. All the T. denticola-infected male and female mice at 8- and 16 weeks demonstrated bacterial colonization (100%) on the gingival surface, and an increase in alveolar bone resorption (p &lt; 0.0001). A total of 70 miRNAs with at least 1.0-fold differential expression/regulation (DE) miRNAs (26 upregulated and 44 downregulated) were identified. nCounter miRNA expression profiling identified 13 upregulated miRNAs (e.g. miR-133a, miR-378) and 25 downregulated miRNAs (e.g. miR-375, miR-34b-5p) in T. denticola-infected mice mandibles during 8-weeks infection whereas 13 upregulated miRNAs (e.g. miR-486, miR-126-5p) and 19 downregulated miRNAs (miR-2135, miR-142-3p) were observed during 16- weeks of infection. One miRNA (miR-126-5p) showed significant difference between 8-and 16-weeks of infection. Interestingly, miR-126-5p has been presented as a potential biomarker in patients with periodontitis and coronary artery disease. Among the 13 upregulated miRNAs, miR-486, miR-126-3p, miR-126-5p were reported in human gingival plaques samples with periodontitis. KEGG analysis revealed various functional pathways of DE miRNAs such as bacterial invasion of epithelial cells, Ras signaling, Fc gamma R- mediated phagocytosis, osteoclast differentiation, adherens signaling and ubiquitin mediated proteolysis. This is the first study of DE miRNAs in mice mandibles at different time-points of T. denticola infection and the combination of three specific miRNAs miR-486, miR-126-3p, miR-126-5p may serve as an invasive biomarker of T. denticola in PD. These miRNAs may have significant role in PD pathogenesis and establishes a link between miRNA, periodontitis, and systemic diseases.

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Global Noncoding microRNA Profiling in Mice Infected with Partial Human Mouth Microbes (PAHMM) Using an Ecological Time-Sequential Polybacterial Periodontal Infection (ETSPPI) Model Reveals Sex-Specific Differential microRNA Expression

Cited by 6 publications

References 67 publications

Streptococcus gordonii Supragingival Bacterium Oral Infection-Induced Periodontitis and Robust miRNA Expression Kinetics

Streptococcus gordonii Supragingival Bacterium Oral Infection-Induced Periodontitis and Robust miRNA Expression Kinetics

The Evaluation of a 5-miRNA Panel in Patients with Periodontitis Disease

Oral Spirochete <em>Treponema denticola </em>Intraoral Infection Reveals Unique miR-133a, miR-486, miR-126-3p, miR-126-5p miRNA Expression Kinetics during Periodontitis

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