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23 pages, 3225 KiB

Open AccessArticle

Temporal Transcriptomic Analysis of Periodontal Disease Progression and Its Molecular Links to Systemic Diseases

by Teerachate Nantakeeratipat, Chiharu Fujihara and Masahide Takedachi

Int. J. Mol. Sci. 2025, 26(5), 1998; https://doi.org/10.3390/ijms26051998 - 25 Feb 2025

Viewed by 451

Abstract

Periodontal disease, a prevalent oral inflammatory condition, is implicated in exacerbating systemic diseases. However, the molecular mechanisms underlying this association remain unclear. In this study, we performed RNA sequencing of gingival tissue samples collected from a mouse model of periodontal disease at multiple [...] Read more.

Periodontal disease, a prevalent oral inflammatory condition, is implicated in exacerbating systemic diseases. However, the molecular mechanisms underlying this association remain unclear. In this study, we performed RNA sequencing of gingival tissue samples collected from a mouse model of periodontal disease at multiple time points to investigate dynamic transcriptomic changes during disease progression. Our analysis revealed distinct temporal gene expression patterns associated with the key inflammatory and immune response pathways. These findings suggest stepwise molecular progression in the periodontal inflammatory process, potentially contributing to systemic inflammation through shared signaling networks. We further identified specific genes and pathways that may mediate the bidirectional relationship between periodontal disease and systemic conditions such as cardiovascular disease and diabetes. By elucidating the temporal dynamics of molecular changes in periodontal disease, this study provides insights into the pathogenesis and its systemic implications. It identifies potential biomarkers and therapeutic targets for local and systemic disease management. Full article

(This article belongs to the Special Issue Oral and Dental Infectious Diseases: Molecular Pathology, Diagnosis and Therapy)

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12 pages, 883 KiB

Open AccessArticle

Antibacterial Activity of Banglene Extracted from Indonesian Ginger “Bangle” Against Porphyromonas gingivalis

by Mayu Sebe, Satoka Senoura, Kiyoshi Miura, Wako Kobayashi, Nagisa Yano, Gaku Yamauchi, Kenichi Harada, Yoshiyasu Fukuyama, Miwa Kubo and Keiji Murakami

Int. J. Mol. Sci. 2025, 26(5), 1787; https://doi.org/10.3390/ijms26051787 - 20 Feb 2025

Viewed by 528

Abstract

Periodontitis is one of the most common diseases associated with the lifestyle habits of adults and is caused by the formation of biofilms, called dental plaques, in periodontal pockets by oral bacteria, such as Porphyromonas gingivalis. Bangle, Zingiber purpureum Rosc. (Indonesian ginger), [...] Read more.

Periodontitis is one of the most common diseases associated with the lifestyle habits of adults and is caused by the formation of biofilms, called dental plaques, in periodontal pockets by oral bacteria, such as Porphyromonas gingivalis. Bangle, Zingiber purpureum Rosc. (Indonesian ginger), a native Indonesian plant, has been traditionally consumed as food and medicine across Southeast Asia. The cis- and trans-banglenes, components of the rhizomes of Z. purpureum, have been reported to possess neurotrophic activity. Hexane extract of bangle exhibited antibacterial activity against P. gingivalis, with a minimum inhibitory concentration of 8 μg/mL. We isolated several compounds from the active fractions through the bioassay-guided isolation of hexane extract. Further, we found that c- and t-banglene inhibited the growth of P. gingivalis at 4 µg/mL; however, these compounds showed no antibacterial effects against oral microorganisms. We also observed that c- and t-banglenes resulted in 47% and 40% reductions in biofilm formation. In conclusion, our results suggest that banglene has specific antibacterial effects against the periodontopathogen P. gingivalis, with minimal impact on oral microorganisms. Thus, banglene has potential applications in the prevention of periodontitis without the risk of substituted microbisms. Full article

(This article belongs to the Special Issue Oral and Dental Infectious Diseases: Molecular Pathology, Diagnosis and Therapy)

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18 pages, 1764 KiB

Open AccessArticle

Exploring the Genetic and Functional Diversity of Porphyromonas gingivalis Survival Factor RagAB

by Pauline G. Montz, Evdokia Dafni, Bernd Neumann, Dongmei Deng, Mohamed M. H. Abdelbary and Georg Conrads

Int. J. Mol. Sci. 2025, 26(3), 1073; https://doi.org/10.3390/ijms26031073 - 26 Jan 2025

Viewed by 967

Abstract

Porphyromonas gingivalis is a key pathogen in periodontitis. Its outer membrane contains the RagAB transport complex, which has been implicated in protein uptake, essential for a proteolytic species. RagA is a 22-stranded β-barrel, and RagB is the corresponding 4-TPR lid, together forming a [...] Read more.

Porphyromonas gingivalis is a key pathogen in periodontitis. Its outer membrane contains the RagAB transport complex, which has been implicated in protein uptake, essential for a proteolytic species. RagA is a 22-stranded β-barrel, and RagB is the corresponding 4-TPR lid, together forming a TonB-dependent system acting as a “pedal bin”. Four different alleles were observed, of which ragAB-1 is more virulent than the others. Our aim was to map ragAB in 129 strains of P. gingivalis and related species available in our collection, supported by a newly introduced universal PCR for amplification/sequencing of all four ragA variants and to find reasons for the differences in virulence and/or fitness. Regarding the PCR method, by pairing established Long-PCR primers with our newly designed sequencing primers (ragA-F0, -F1, -R2, -R2a, -R4), it was possible to amplify and sequence all four ragA variants. The same was not possible for ragB due to high heterogeneity. The mapping allowed us to type all strains into ragAB-1-4. For each type, some strains (of mainly animal origin such as Porphyromonas gulae) with slightly different amino acid sequences were identified (designated ragAB-1a to -4a). In terms of function, the transfer of recently discovered SusCD information to the similar RagAB complex provided new insights. Substrate specificity as well as length of pedal could be the route to differential virulence (survival rate, fitness) as Rag-1 (closer related to Rag-3/4) and Rag-2 were found to be massively different here. In general, substrate–ligand-binding sites seem to be quite variable with the exception of Rag-1, probably indicating nutritional preferences. In addition, an insertion (8 aa long) found in loop L7 throughout RagA-2 could not only affect the dynamics of lid opening/closing but might also alter the associated substrate throughput rate. Full article

(This article belongs to the Special Issue Oral and Dental Infectious Diseases: Molecular Pathology, Diagnosis and Therapy)

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11 pages, 644 KiB

Open AccessArticle

Real-Time PCR Method as Diagnostic Tool for Detection of Periodontal Pathogens in Patients with Periodontitis

by Sendi Kuret, Nina Kalajzic, Matija Ruzdjak, Blaženka Grahovac, Marina Adriana Jezina Buselic, Sanda Sardelić, Anja Delic, Lana Susak and Davorka Sutlovic

Int. J. Mol. Sci. 2024, 25(10), 5097; https://doi.org/10.3390/ijms25105097 - 7 May 2024

Cited by 1 | Viewed by 2560

Abstract

The most common type of periodontal disease is chronic periodontitis, an inflammatory condition caused by pathogenic bacteria in subgingival plaque. The aim of our study was the development of a real-time PCR test as a diagnostic tool for the detection and differentiation of [...] Read more.

The most common type of periodontal disease is chronic periodontitis, an inflammatory condition caused by pathogenic bacteria in subgingival plaque. The aim of our study was the development of a real-time PCR test as a diagnostic tool for the detection and differentiation of five periodontopathogenic bacteria, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, and Treponema denticola, in patients with periodontitis. We compared the results of our in-house method with the micro-IDent^® semiquantitative commercially available test based on the PCR hybridization method. DNA was isolated from subgingival plaque samples taken from 50 patients and then analyzed by both methods. Comparing the results of the two methods, they show a specificity of 100% for all bacteria. The sensitivity for A. actinomycetemcomitans was 97.5%, for P. gingivalis 96.88%, and for P. intermedia 95.24%. The sensitivity for Tannerella forsythia and T. denticola was 100%. The Spearman correlation factor of two different measurements was 0.976 for A. actinomycetemcomitans, 0.967 for P. gingivalis, 0.949 for P. intermedia, 0.966 for Tannerella forsythia, and 0.917 for T. denticola. In conclusion, the in-house real-time PCR method developed in our laboratory can provide information about relative amount of five bacterial species present in subgingival plaque in patients with periodontitis. It is likely that such a test could be used in dental diagnostics in assessing the efficacy of any treatment to reduce the bacterial burden. Full article

(This article belongs to the Special Issue Oral and Dental Infectious Diseases: Molecular Pathology, Diagnosis and Therapy)

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17 pages, 4527 KiB

Open AccessArticle

Inhibitory Effect of Adsorption of Streptococcus mutans onto Scallop-Derived Hydroxyapatite

by Momoko Usuda, Mariko Kametani, Masakazu Hamada, Yuto Suehiro, Saaya Matayoshi, Rena Okawa, Shuhei Naka, Michiyo Matsumoto-Nakano, Tatsuya Akitomo, Chieko Mitsuhata, Kazuya Koumoto, Keiko Kawauchi, Takahito Nishikata, Masatoshi Yagi, Toshiro Mizoguchi, Koki Fujikawa, Taizo Taniguchi, Kazuhiko Nakano and Ryota Nomura

Int. J. Mol. Sci. 2023, 24(14), 11371; https://doi.org/10.3390/ijms241411371 - 12 Jul 2023

Cited by 11 | Viewed by 2204

Abstract

Hydroxyapatite adsorbs various substances, but little is known about the effects on oral bacteria of adsorption onto hydroxyapatite derived from scallop shells. In the present study, we analyzed the effects of adsorption of Streptococcus mutans onto scallop-derived hydroxyapatite. When scallop-derived hydroxyapatite was mixed [...] Read more.

Hydroxyapatite adsorbs various substances, but little is known about the effects on oral bacteria of adsorption onto hydroxyapatite derived from scallop shells. In the present study, we analyzed the effects of adsorption of Streptococcus mutans onto scallop-derived hydroxyapatite. When scallop-derived hydroxyapatite was mixed with S. mutans, a high proportion of the bacterial cells adsorbed onto the hydroxyapatite in a time-dependent manner. An RNA sequencing analysis of S. mutans adsorbed onto hydroxyapatite showed that the upregulation of genes resulted in abnormalities in pathways involved in glycogen and histidine metabolism and biosynthesis compared with cells in the absence of hydroxyapatite. S. mutans adsorbed onto hydroxyapatite was not killed, but the growth of the bacteria was inhibited. Electron microscopy showed morphological changes in S. mutans cells adsorbed onto hydroxyapatite. Our results suggest that hydroxyapatite derived from scallop shells showed a high adsorption ability for S. mutans. This hydroxyapatite also caused changes in gene expression related to the metabolic and biosynthetic processes, including the glycogen and histidine of S. mutans, which may result in a morphological change in the surface layer and the inhibition of the growth of the bacteria. Full article

(This article belongs to the Special Issue Oral and Dental Infectious Diseases: Molecular Pathology, Diagnosis and Therapy)

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11 pages, 2216 KiB

Open AccessArticle

MiR-424/TGIF2-Mediated Pro-Fibrogenic Responses in Oral Submucous Fibrosis

by Ming-Yung Chou, Pei-Ling Hsieh, Shih-Chi Chao, Yi-Wen Liao, Cheng-Chia Yu and Chang-Yi Tsai

Int. J. Mol. Sci. 2023, 24(6), 5811; https://doi.org/10.3390/ijms24065811 - 18 Mar 2023

Cited by 14 | Viewed by 2491

Abstract

Oral submucous fibrosis (OSF) has been recognized as a potentially malignant disorder and is characterized by inflammation and the deposition of collagen. Among various regulators of fibrogenesis, microRNAs (miR) have received great attention but the detailed mechanisms underlying the miR-mediated modulations remain largely [...] Read more.

Oral submucous fibrosis (OSF) has been recognized as a potentially malignant disorder and is characterized by inflammation and the deposition of collagen. Among various regulators of fibrogenesis, microRNAs (miR) have received great attention but the detailed mechanisms underlying the miR-mediated modulations remain largely unknown. Here, we showed that miR-424 was aberrantly overexpressed in OSF tissues, and then we assessed its functional role in the maintenance of myofibroblast characteristics. Our results demonstrated that the suppression of miR-424 markedly reduced various myofibroblast activities (such as collagen contractility and migration ability) and downregulated the expression of fibrosis markers. Moreover, we showed that miR-424 exerted this pro-fibrosis property via direct binding to TGIF2, an endogenous repressor of the TGF-β signaling. In addition, our findings indicated that overexpression of miR-424 activated the TGF-β/Smad pathway, leading to enhanced myofibroblast activities. Altogether, our data revealed how miR-424 contributed to myofibroblast transdifferentiation, and targeting the miR-424/TGIF2 axis may be a viable direction for achieving satisfactory results from OSF treatment. Full article

(This article belongs to the Special Issue Oral and Dental Infectious Diseases: Molecular Pathology, Diagnosis and Therapy)

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Review

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14 pages, 384 KiB

Open AccessReview

Inflammatory Mediators in the Oral Fluids and Blood Samples of Type 1 Diabetic Patients, According to Periodontal Status—A Systematic Review

by Álvaro Parra Meder, Rosana Costa, Paula López-Jarana, Blanca Ríos-Carrasco, Marta Relvas and Filomena Salazar

Int. J. Mol. Sci. 2025, 26(6), 2552; https://doi.org/10.3390/ijms26062552 - 12 Mar 2025

Cited by 1 | Viewed by 499

Abstract

There is currently little information on the immune profile of adult type 1 diabetes patients diagnosed with periodontal disease. The aim of this systematic review is to bring together the known evidence of which inflammatory markers, measured in salivary flow or gingival crevicular [...] Read more.

There is currently little information on the immune profile of adult type 1 diabetes patients diagnosed with periodontal disease. The aim of this systematic review is to bring together the known evidence of which inflammatory markers, measured in salivary flow or gingival crevicular fluid and serum blood, are present in both pathologies. Following the Preferred Reporting Items for Systematic reviews and Meta-Analys guidelines, we systematically searched in the PubMed, Web of Science, Scopus and Cochrane Library databases for studies on the associations of different chemokines with type 1 diabetes mellitus and periodontal disease. From a total of 703 patients, of which 526 were patients diagnosed with type 1 diabetes and 215 were controls without diabetes, multiple inflammatory mediators, such as interleukin 8, which showed higher concentrations in the crevicular fluid in several studies of type 1 diabetes patients and a greater severity in its effects on the periodontal status, as well as osteoprotegerin and tumor necrosis factor alpha, have been found elevated in diabetic patients with poor periodontal control. The results suggest that interleukin 8, tumor necrosis factor alpha and osteoprotegerin may be promising novel biomarkers of type 1 diabetes mellitus, and may also indicate the susceptibility profile in these individuals for the worsening of the patient’s periodontal status. Full article

(This article belongs to the Special Issue Oral and Dental Infectious Diseases: Molecular Pathology, Diagnosis and Therapy)

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12 pages, 699 KiB

Open AccessReview

Periodontitis Disease in Farmed Ruminants—Current State of Research

by Arkadiusz Grzeczka, Marianna Lech, Gracjan Wozniak, Szymon Graczyk, Pawel Kordowitzki, Małgorzata Olejnik, Marek Gehrke and Jędrzej Maria Jaśkowski

Int. J. Mol. Sci. 2023, 24(11), 9763; https://doi.org/10.3390/ijms24119763 - 5 Jun 2023

Cited by 5 | Viewed by 2502

Abstract

Periodontal disease in ruminants is common and occurs in farmed and wild animals. Periodontal lesions can result from the secretion of endotoxins by pathogenic bacteria and as consequences of immune system activity. Three main types of periodontitis have been described. The first is [...] Read more.

Periodontal disease in ruminants is common and occurs in farmed and wild animals. Periodontal lesions can result from the secretion of endotoxins by pathogenic bacteria and as consequences of immune system activity. Three main types of periodontitis have been described. The first is chronic inflammation involving mainly premolars and molars—periodontitis (PD). The second type is an acute inflammatory reaction occurring with calcification of the periosteum of the jawbone and swelling of the surrounding soft tissues (Cara inchada, CI—“swollen face”). Finally, a third type, similar to the first but located in the incisor area, is called “broken mouth” (BM). Etiological variation between the different types of periodontitis is indicated. This particularly manifests in the composition of the microbiome, which is characteristic of the different forms of periodontitis. The widespread detection of lesions has drawn attention to the current nature of the problem. Full article

(This article belongs to the Special Issue Oral and Dental Infectious Diseases: Molecular Pathology, Diagnosis and Therapy)

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