Gingival Tissue MiRNA Expression Profiling and an Analysis of Periodontitis-Specific Circulating MiRNAs.

This study aimed to identify the microRNAs (miRNAs) associated with periodontitis (PD) in gingival tissues, and to evaluate the levels of these selected miRNAs in the saliva and blood plasma among participants with and without rheumatoid arthritis (RA). A genome-wide miRNA expression analysis in 16 gingival tissue samples revealed 177 deregulated miRNAs. The validation of the miRNA profiling results in 80 gingival tissue samples revealed that the PD-affected tissues had a higher expression of miR-140-3p and -145-5p, while the levels of miR-125a-3p were significantly lower in inflamed tissues. After a thorough validation, four miRNAs, namely miR-140-3p, -145-5p, -146a-5p, and -195-5p, were selected for further analysis in a larger sample of salivary (N = 173) and blood plasma (N = 221) specimens. Increased salivary levels of miR-145-5p were associated with higher mean values of pocket probing depth and bleeding on probing index. The plasma-derived levels of miR-140-3p were higher among the participants with PD. In conclusion, the gingival levels of miR-140-3p, -145-5p, and -125a-3p were independently associated with PD presence and severity. The salivary and blood plasma levels of the target miRNAs were diversely related to PD. Similar miRNA associations with PD were observed among the participants with and without RA.

Gingival crevicular fluid microRNA associations with periodontitis.

PURPOSE: The present study was performed to assess the associations of gingival crevicular fluid (GCF) microRNAs miR-140-3p, miR-145-5p, miR-146a-5p, and miR-195-5p with periodontitis (PD) and to evaluate the possible influence of rheumatoid arthritis (RA) in this context. METHOD: GCF samples were collected from 134 individuals with PD and 76 periodontally healthy individuals, with or without RA. After miRNA extraction from GCF, the levels of miR-140-3p, miR-145-5p, miR-146a-5p, and miR-195-5p were assessed using RT-qPCR. RESULTS: MiR-146a-5p levels were significantly lower among the patients with PD than among the healthy individuals (P < 0.001) and negatively correlated with PD severity based on PD stage and periodontal outcome parameters (P < 0.05). Patients with severe PD had higher GCF levels of miR-140-3p and miR-145-5p than did periodontally healthy individuals (P < 0.05). Significant AUC values for diagnosis of severe PD were revealed for miR-140-3p (AUC = 0.614, P = 0.022), miR-145-5p (AUC = 0.621, P = 0.016) and miR-146a-5p (AUC = 0.702, P < 0.001). Combination of the aforementioned miRNAs increased the diagnostic performance (AUC = 0.709, P < 0.001). CONCLUSION: It was demonstrated that miR-140-3p, miR-145-5p and miR-146a-5p were associated with PD and would be potentially effective for GCF-based non-invasive periodontitis diagnostics in patients with and without RA.

Analysis of periodontitis-associated miRNAs in gingival tissue, gingival crevicular fluid, saliva and blood plasma.

OBJECTIVE: Periodontitis (PD) is a chronic inflammatory disease which is associated with multiple systemic comorbidities, including rheumatoid arthritis (RA), meanwhile the etiopathology of PD may be modulated by various factors including microRNA (miRNA). The present study aimed to reveal miRNAs associated with PD in gingival tissue, gingival crevicular fluid (GCF), saliva, plasma and to assess the possible influence of RA. DESIGN: The cross-sectional study included 30 patients with PD and 31 periodontally healthy participants. A total of 25 participants were additionally diagnosed with RA. Microarray analysis of eight gingival tissue samples was performed and four PD-associated miRNAs were selected: miR-199a-5p, miR-483-5p, miR-3198 and miR-4299. Target miRNAs were further assessed by means of RT-qPCR in 61 gingival tissue samples and corresponding bodily fluids - GCF, saliva and plasma. RESULTS: The upregulation of miR-199a-5p and downregulation of miR-4299 in gingival tissue was associated with the presence of PD and RA (P < 0.05). GCF level of miR-3198 was higher amongst participants with PD (P = 0.019) and showed a good diagnostic ability (AUC = 0.72, P = 0.008). Increased miR-199a-5p salivary level and decreased miR-199a-5p plasma level were observed amongst patients with worse clinical status of PD (P < 0.05). MiR-3198 and miR-4299 combination in GCF demonstrated AUC value of 0.86 and reached sensitivity of 68 % and specificity of 96 %. CONCLUSIONS: Aberrant expression of miR-199a-5p, miR-483-5p, miR-3198, miR-4299 in gingival tissues is associated with the presence and/or severity of PD. MiR-3198, miR-4299 level in GCF and miR-199a-5p level in plasma strongly correlated with PD, demonstrating significant diagnostic performance.

Associations of periodontal status in periodontitis and rheumatoid arthritis patients.

PURPOSE: The aim of this study was to assess the association between the clinical status of rheumatoid arthritis (RA) and periodontitis (PD) in patients diagnosed with PD and to evaluate the impact of RA treatment on the severity of PD. METHODS: The study included 148 participants with PD, of whom 64 were also diagnosed with RA (PD+RA group), while 84 age-matched participants were rheumatologically healthy (PD-only group). PD severity was assessed by the following periodontal parameters: clinical attachment loss, probing pocket depth (PPD), bleeding on probing (BOP), alveolar bone loss, and number of missing teeth. RA disease characteristics and impact of disease were evaluated by the Disease Activity Score 28 using C-reactive protein, disease duration, RA treatment, the RA Impact of Disease tool, and the Health Assessment Questionnaire. Outcome variables were compared using parametric and non-parametric tests and associations were evaluated using regression analysis with the calculation of odds ratios (ORs). RESULTS: Participants in the PD+RA group had higher mean PPD values (2.81 ± 0.59 mm vs. 2.58 ± 0.49 mm, P=0.009) and number of missing teeth (6.27±4.79 vs. 3.93±4.08, P=0.001) than those in the PD-only group. A significant association was found between mean PPD and RA (OR, 2.22; 95% CI, 1.16-4.31; P=0.016). Within the PD+RA group, moderate to severe periodontal disease was significantly more prevalent among participants with higher RA disease activity (P=0.042). The use of biologic disease-modifying antirheumatic drugs (bDMARDs) was associated with a lower BOP percentage (P=0.016). CONCLUSIONS: In patients with PD, RA was associated with a higher mean PPD and number of missing teeth. The severity of PD was affected by the RA disease clinical activity and by treatment with bDMARDs, which were associated with a significantly lower mean BOP percentage.

Investigating the relationship between the severity of periodontitis and rheumatoid arthritis: a cross-sectional study.

OBJECTIVES: This paper evaluates the prevalence and severity of periodontitis (PD) in patients with rheumatoid arthritis (RA), focusing on the link between the severity of PD with RA disease activity/disability scores, the influence of RA treatment on PD, and levels of vitamin D. METHODS: A total of 93 RA patients were enrolled in the cross-sectional study and analyzed accordingly as RA-PD (N = 63, 67.8%) and RA-only (N = 30, 32.2%) groups. A number of associations between rheumatological clinical data, i.e., Disease Activity Score (DAS28 CRP), health assessment questionnaires, and PD severity (measured by periodontal outcome parameters) with regard to serum levels of vitamin D were assessed. The outcome variables were compared by parametric and non-parametric tests. RESULTS: A total of 29% of RA patients were diagnosed with severe PD. The RA-PD group presented a higher mean DAS28 CRP score in moderate-severe PD compared to periodontally healthy-initial stage PD subjects (4.49 ± 1.22 vs. 3.86 ± 1.58, p = 0.033). RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) were less likely to be diagnosed with PD (p = 0.022) and revealed significantly lower PD outcome parameters, i.e., bleeding on probing (%) and bone loss (%) (p < 0.05). Vitamin D concentration was significantly lower in RA-PD group with diagnosed advanced severe PD (IV stage) compared to moderate PD (II stage) (39.61 ± 17.12 vs. 52.07 ± 18.23 nmol/l, p = 0.031). CONCLUSIONS: The study revealed a high prevalence of severe PD in RA patients, being significantly associated with higher RA disease activity and lower vitamin D level in RA-PD group, while bDMARD treatment was related to lower PD outcome parameters. Key Points • Severe PD is prevalent amongst RA patients and is associated with RA disease activity. The higher RA DAS28 CRP score is associated with moderate-severe PD compared to periodontally healthy-initial stage PD in RA patients. • Biologic DMARDs treatment used for RA is linked to lower PD rates and PD outcome parameters. • Significantly lower vitamin D level is found in advanced severe PD compared to moderate PD stage in RA-PD subjects.