Drug-induced gingival overgrowth is caused by the antiseizure medication phenytoin, calcium channel blockers, and ciclosporin. Characteristics of these drug-induced gingival overgrowth lesions differ. We evaluate the ability of a mouse model to mimic human phenytoin-induced gingival overgrowth and assess the ability of a drug to prevent its development. Lovastatin was chosen based on previous analyses of tissue-specific regulation of CCN2 production in human gingival fibroblasts and the known roles of CCN2 in promoting fibrosis and epithelial to mesenchymal transition. Data indicate that anterior gingival tissue overgrowth occurred in phenytoin-treated mice based on gross tissue observations and histomorphometry of tissue sections. Molecular markers of epithelial plasticity and fibrosis were regulated by phenytoin in gingival epithelial tissues and in connective tissues similar to that seen in humans. Lovastatin attenuated epithelial gingival tissue growth in phenytoin-treated mice and altered the expressions of markers for epithelial to mesenchymal transition. Data indicate that phenytoin-induced gingival overgrowth in mice mimics molecular aspects of human gingival overgrowth and that lovastatin normalizes the tissue morphology and the expression of the molecular markers studied. Data are consistent with characterization of phenytoin-induced human gingival overgrowth in vivo and in vitro characteristics of cultured human gingival epithelial and connective tissue cells. Findings suggest that statins may serve to prevent or attenuate phenytoin-induced human gingival overgrowth, although specific human studies are required.

Connective tissue growth factor (CCN2/CTGF) mediates transforming growth factor-β (TGF-β)-induced fibrosis. Drug-induced gingival overgrowth is tissue specific. Here the role of the phosphoinositol 3-kinase (PI3K) pathway in mediating TGF-β1-stimulated CCN2/CTGF expression in primary human adult gingival fibroblasts and human adult lung fibroblasts was compared. Data indicate that PI3K inhibitors attenuate upregulation of TGF-β1-induced CCN2/CTGF expression in human gingival fibroblasts independent of reducing JNK MAP kinase activation. Pharmacologic inhibitors and small interfering (si)RNA-mediated knockdown studies indicate that calcium-dependent isoforms and an atypical isoform of protein kinase C (PKC-δ) do not mediate TGF-β1-stimulated CCN2/CTGF expression in gingival fibroblasts. As glycogen synthase kinase-3β (GSK-3β) can undergo phosphorylation by the PI3K/pathway, the effects of GSK-3β inhibitor kenpaullone and siRNA knockdown were investigated. Data in gingival fibroblasts indicate that kenpaullone attenuates TGF-β1-mediated CCN2/CTGF expression. Activation of the Wnt canonical pathways with Wnt3a, which inhibits GSK-3β, similarly inhibits TGF-β1-stimulated CCN2/CTGF expression. In contrast, inhibition of GSK-3β by Wnt3a does not inhibit, but modestly stimulates, CCN2/CTGF levels in primary human adult lung fibroblasts and is β-catenin dependent, consistent with previous studies performed in other cell models. These data identify a novel pathway in gingival fibroblasts in which inhibition of GSK-3β attenuates CCN2/CTGF expression. In adult lung fibroblasts inhibition of GSK-3β modestly stimulates TGF-β1-regulated CCN2/CTGF expression. These studies have potential clinical relevance to the tissue specificity of drug-induced gingival overgrowth.

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BACKGROUND: The occurrence of periodontitis is rather infrequent in children and adolescence and increases with age. We conducted this study because there have been few epidemiological studies on prevalence of periodontitis in children in Saudi Arabia. OBJECTIVE: Determine the prevalence of periodontitis in high school children in Saudi Arabia. DESIGN: Cross-sectional, using cluster and multistage sampling. SETTING: High school children in Saudi Arabia. PARTICIPANTS AND METHODS: Periodontal examinations were conducted on a randomized sample of high school children between the ages 15 to 19 in Saudi Arabia. The study spanned from September 2012 to January 2016. Clinical examinations included measurements of the probing depth (PD) percentage of PD ≥4 mm per patient. MAIN OUTCOME MEASURES: The prevalence of periodontitis (PD ≥4 mm and CAL ≥1 mm), the mean percentage PD ≥4 mm, the mean percentage CAL ≥1 mm, plaque index (PI) and gingival index (GI). SAMPLE SIZE: 2435 high school students. RESULTS: Of 2435 high school children in the sample, 209 students (8.6%) had periodontitis. The mean (standard deviation) for the PD was 0.59 (0.17) mm. Differences in percentage PD ≥4 mm and CAL ≥1 mm were greater in students with periodontitis ( P <.001). The prevalence of periodontitis was higher among non-Saudis, students who did not brush their teeth and did not visit their dentist regularly. In the bivariate analysis, periodontitis was positively associated with GI, PI, number of teeth extracted, mean percentage PD ≥4 mm, and mean PD. However, in the multivariate analysis, tooth brushing was the main factor protective against periodontitis (odds ratio: 0.62, 95% CI 0.42-0.92, P =.017). CONCLUSION: Periodontitis prevalence was high compared with Western countries in a nationally representative sample of high school students in Saudi Arabia. LIMITATIONS: Partial mouth study design, which may underestimate the disease prevalence. CONFLICT OF INTEREST: None.

Glycemic control appears to have a significant impact on the relationship between periodontitis and diabetes. The current study aimed to investigate the association between the stage of periodontitis and hemoglobin A1c (HbA1c) levels in patients considered to be normoglycemic. A total of 135 patients (100 females and 35 males) with no history of diabetes were included in the study. The mean age of the participants was 38.4 years old. All patients underwent a full-mouth periodontal examination. Periodontal diagnosis was determined according to the 2017 World Workshop on the Classification of Periodontal Disease. The glycemic state of the patients was assessed using a chair-side HbA1c analyzer. Ninety patients were diagnosed with periodontitis. Higher average HbA1c levels were associated with the different stages of periodontitis (p<0.01). Most of the non-periodontitis patients were in the non-diabetes group (67%), while most of the periodontitis patients were in the undiagnosed pre-diabetes group (47% of the stages I and II group, and 44% of the stages III and IV groups) (p<0.001). Periodontitis was found to be significantly associated with elevated glycated hemoglobin levels in patients not previously diagnosed with diabetes, and the elevation in HbA1c levels was more evident in patients with stage III and IV periodontitis.