Periodontitis, pathogenesis and progression: miRNA-mediated cellular responses to<i>Porphyromonas gingivalis</i>

Olsen, Ingar; Singhrao, Simarjit Kaur; Osmundsen, Harald

doi:10.1080/20002297.2017.1333396

Cited by 33 publications

(36 citation statements)

References 40 publications

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“…Thus, there is now compelling evidence that miRNAs are associated with physiological and pathological process that contribute to the development and progression of systemic diseases, such as cancers [33] and vascular disease [34], as well as periodontal disease [22,35]. Several studies described the potential of miRNAs as putative diagnostic biomarkers for periodontal disease, including hsa-miR-15a-5p, hsa-miR-29b-3p, hsa-miR-124-3p, hsa-miR-140-5p, hsa-miR-146a-5p, hsa-miR-148a-3p, hsa-miR-155-5p, hsa-miR-223-3p, hsa-miR-301b, hsa-miR-628-5p [21][22][23][24][25][26]. It has been reported that hsa-miR-140-5p and hsa-miR-628-5p in gingival crevicular fluid are potential diagnostic biomarkers for periodontitis [25].…”

Section: Discussionmentioning

confidence: 99%

“…However, no studies have explored miRNAs' expression patterns in salivary sEVs as potential biomarkers for periodontal status. According to published reviews [21][22][23][24][25][26], ten periodontitis-associated miRNAs (hsa-miR-15a-5p, hsa-miR-29b-3p, hsa-miR-124-3p, hsa-miR-140-5p, hsa-miR-146a-5p, hsa-miR-148a-3p, hsa-miR-155-5p, hsa-miR-223-3p, hsa-miR-301b, hsa-miR-628-5p) have been explored as potential periodontitis biomarkers from one or more sample sources, such as saliva, gingival tissues, or periodontium-derived cells. However, since miRNAs are expressed in a tissue and biofluid-specific manner, it is important to investigate whether these proposed miRNA periodontitis biomarker candidates are also expressed in salivary sEVs.…”

Section: Introductionmentioning

confidence: 99%

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Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status—A Pilot Study

Han

Bartold

Salomón

et al. 2020

IJMS

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This pilot study aims to investigate whether salivary small extracellular vesicle (sEV)-associated microRNAs could act as potential biomarkers for periodontal disease status. Twenty-nine participants (10 who were healthy, nine with gingivitis, 10 with stage III/IV periodontitis) were recruited and unstimulated whole saliva samples were collected. Salivary sEVs were isolated using the size-exclusion chromatography (SEC) method and characterised by morphology, EV-protein and size distribution using transmission electron microscopy (TEM), Western Blot and Nanoparticle Tracking Analysis (NTA), respectively. Ten mature microRNAs (miRNAs) in salivary sEVs and saliva were evaluated using RT-qPCR. The discriminatory power of miRNAs as biomarkers in gingivitis and periodontitis versus healthy controls was evaluated by Receiver Operating Characteristics (ROC) curves. Salivary sEVs were comparable to sEVs morphology, mode, size distribution and particle concentration in healthy, gingivitis and periodontitis patients. Compared to miRNAs in whole saliva, three significantly increased miRNAs (hsa-miR-140-5p, hsa-miR-146a-5p and hsa-miR-628-5p) were only detected in sEVs in periodontitis when compared to that of healthy controls, with a good discriminatory power (area under the curve (AUC) = 0.96) for periodontitis diagnosis. Our study demonstrated that salivary sEVs are a non-invasive source of miRNAs for periodontitis diagnosis. Three miRNAs that are selectively enriched in sEVs, but not whole saliva, could be potential biomarkers for periodontal disease status.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status—A Pilot Study

Han

Bartold

Salomón

et al. 2020

IJMS

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“…Agents that can impede apoptosis may promote the build-up of cancerous cells [26]. In addition, miRNA-203 from P. gingivalis suppresses SOC6 that has an important role in modulating mitochondrial dynamics and subsequent apoptotic events [70,71]. Regulation of the cell cycle by miR-203 may affect the pathological expression in some carcinomas [72].…”

Section: Porphyromonas Gingivalis Accelerates Cell Cycling and Supprementioning

confidence: 99%

Possible role of Porphyromonas gingivalis in orodigestive cancers

Olsen

Yılmaz

2019

Journal of Oral Microbiology

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138

117

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There is increasing evidence for an association between periodontitis/tooth loss and oral, gastrointestinal, and pancreatic cancers. Periodontal disease, which is characterized by chronic inflammation and microbial dysbiosis, is a significant risk factor for orodigestive carcinogenesis. Porphyromonas gingivalis is proposed as a keystone pathogen in chronic periodontitis causing both dysbiosis and discordant immune response. The present review focuses on the growing recognition of a relationship between P. gingivalis and orodigestive cancers. Porphyromonas gingivalis has been recovered in abundance from oral squamous cell carcinoma (OSCC). Recently established tumorigenesis models have indicated a direct relationship between P. gingivalis and carcinogenesis. The bacterium upregulates specific receptors on OSCC cells and keratinocytes, induces epithelial-to-mesenchymal (EMT) transition of normal oral epithelial cells and activates metalloproteinase-9 and interleukin-8 in cultures of the carcinoma cells. In addition, P. gingivalis accelerates cell cycling and suppresses apoptosis in cultures of primary oral epithelial cells. In oral cancer cells, the cell cycle is arrested and there is no effect on apoptosis, but macro autophagy is increased. Porphyromonas gingivalis promotes distant metastasis and chemoresistance to anti-cancer agents and accelerates proliferation of oral tumor cells by affecting gene expression of defensins, by peptidyl-arginine deiminase and noncanonical activation of β-catenin. The pathogen also converts ethanol to the carcinogenic intermediate acetaldehyde. In addition, P. gingivalis can be implicated in precancerous gastric and colon lesions, esophageal squamous cell carcinoma, head and neck (larynx, throat, lip, mouth and salivary glands) carcinoma, and pancreatic cancer. The fact that distant organs can be involved clearly emphasizes that P. gingivalis has systemic tumorigenic effects in addition to the local effects in its native territory, the oral cavity. Although coinfection with other bacteria, viruses, and fungi occurs in periodontitis, P. gingivalis relates to cancer even in absence of periodontitis. Thus, there may be a direct relationship between P. gingivalis and orodigestive cancers.

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“…Chronic inflammation and the activation of nuclear factor kappa B (NF-κB) are known to be associated with development of multiple cancers (15), while inflammatory cytokines are potent stimulants of miR-146a through NF-κB pathway (16,17). Specifically, several studies report that various miRNAs, including hsa-miR-20a, hsa-miR-142-3p, hsa-miR-19a, hsa-let-7f, hsa-miR-203, hsa-miR-17, hsa-miR-223, hsa-miR-146b and hsa-miR-146a, are highly expressed in patients with periodontitis (18)(19)(20). Furthermore, through regulation of interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling, miR-146a may link the chronic inflammation and cancer (21).…”

Section: Introductionmentioning

confidence: 99%

Functional diversity of miR-146a-5p and TRAF6 in normal and oral cancer cells

Min

Jung

Kang

et al. 2017

International Journal of Oncology

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Numerous studies implicate miR-146a as pleiotropic regulator of carcinogenesis; however, its roles in carcinogenesis are not fully understood. A clue from expression analyses of miR-146a-5p in all 13 oral squamous cell carcinoma (OSCC) cell lines examined and in OSCC tissues, whole blood and whole saliva of OSCC patients in vivo revealed that miR‑146a-5p expression was highly upregulated. Particularly, we widened the view of its upregulation in saliva, implicating that high miR-146a-5p expression is not only correlated closely to the development of human oral cancer, but also to a possible candidate as a diagnostic marker of OSCC. Indeed, further examination showed that exogenous miR-146a-5p expression showed pleiotropic effects on cell proliferation and apoptosis which were partially based on the contextual responses of activation of JNK, downstream of TRAF6 that was targeted by miR-146a-5p in normal human keratinocytes and OSCC cell lines. TRAF6 suppression by a TRAF6-specific siRNA resulted in contradictory consequences on cellular processes in normal and OSCC cells. Notably, TRAF6 downregulation by both miR-146a-5p and TRAF6-specific siRNA deactivated JNK in SCC-9, but not in normal human keratinocytes. In support of the proliferation-promoting effect of miR-146a-5p, silencing of endogenous miR-146a-5p significantly reduced proliferation of SCC-9. Together, these results suggest that miR-146a-5p affects proliferation and apoptosis in a cellular context-dependent manner and selectively disarms the TRAF6-mediated branch of the TGF-β signaling in OSCC cell lines by sparing Smad4 involvement.

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Periodontitis, pathogenesis and progression: miRNA-mediated cellular responses toPorphyromonas gingivalis

Cited by 33 publications

References 40 publications

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status—A Pilot Study

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status—A Pilot Study

Possible role of Porphyromonas gingivalis in orodigestive cancers

Functional diversity of miR-146a-5p and TRAF6 in normal and oral cancer cells

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