Project description:In order to determine the mechanism of the effect of periodontitis on the healing of tooth extraction sockets in mice, the mandibular first molar extraction models of mice in the periodontitis group and the control group were constructed respectively, and samples were taken for RNA-Seq at three time points: 0d, 3d, and 7d. Analysis of key genes in periodontitis regulating tooth extraction socket healing was conducted.
Project description:Background/purpose Periodontal diseases exacerbate hepatic inflammation and diseases like non-alcoholic fatty liver disease via circulating pathogenic factors from periodontal tissue. Long-term pre-symptomatic state eventually leads to the development of such hepatic diseases. However, it is uncertain if periodontitis contributes in the onset of hepatic pre-symptomatic state. Herein, we conducted a hepatic whole transcription analysis of periodontitis-affected mice and healthy mice to understand the early functional changes in the hepatic system in periodontitis-affected mice. Materials and methods Silk ligatures were tied around mice second maxillary molars for 14 days to develop periodontitis. RNA-seq samples were collected from periodontal tissues and liver tissues of mice with periodontitis and healthy mice. Lipidomic analysis of hepatic omega-3 fatty acids in periodontitis-affected and healthy mice was conducted. The anti-inflammatory effects of omega-3 fatty acids and their metabolites were elucidated using hepatocytes HepG2 cells. Results In the liver of mice with periodontitis, genes coding for cytochrome P450 such as Cyp4a12a and Cyp4a12b were identified as significantly down-regulated genes. Lipidomic analyses identified that epoxidation and subsequent hydrolysis of hepatic omega-3 fatty acids were inhibited in periodontitis-affected mice. Eicosapentaenoic acid metabolites, epoxy eicosatetraenoic acid and dihydroxyeicosatetraenoic acid, inhibited inflammatory responses of HepG2 cells. Conclusion These results suggest that, in the liver of periodontitis-affected mice, due to the reduced activity of omega-3 fatty acid epoxidation, pre-symptomatic state with pro-inflammatory status develop. Therefore, early intervention of periodontitis might contribute to the prevention of the onset of hepatic diseases.
Project description:We report the application of high throughput Illumina sequencing for profiling of small RNAs in saliva of patients who were diagnosed with chronic periodontitis as compared to healthy controls. To date, there is no published literature on salivary microRNA profiling done using the high throughput next-generation sequencing analysis in patients diagnosed with chronic periodontitis. Also, this is the first study of its kind done in an Indian population. The objectives of the study were to profile microRNAs expressed in saliva of patients diagnosed with chronic periodontitis, to identify differentially expressed microRNAs between chronic periodontitis and healthy patients and to identify putative salivary microRNAs which can serve as biomarkers for periodontal disease.
Project description:Redondoviridae is a recently identified family of DNA viruses associated with periodontitis. Circular RNAs (circRNAs) emerged as a novel endogenous, conserved noncoding RNAs, which contributed to the virus related immune‐inflammatory response. However, the characteristics and function of circRNAs in Redondoviridae related periodontal inflammation are not yet understood. The present study aimed to analyze the expression profiles of circRNAs in gingival tissues in periodontitis patients with and without Redondoviridae-infection and healthy controls using high-throughput RNA sequencing combined with experimental validation. Out of 17819 circRNAs, 175 circRNAs were dysregulated. Functional annotation and enrichment analysis of the differential circRNAs host genes demonstrated the potential alteration in the molecular and cellular components and metabolism in individuals suffering from periodontitis with Redondoviridae infection. Moreover, “axon guidance” (PATH:04360), “lysine biosynthesis” (PATH:00300) and “vascular endothelial growth factor signaling pathways” (PATH:04370) were significantly enriched in Redondoviridae infected gingivitis tissues. Furthermore, the key circRNAs (circCOL1A1, circAASS, circPTK2, circATP2B4, circDOCK1, circTTBK2, and circMCTP2) associated with the pathobiology of Redondoviridae related periodontitis were revealed by constructing circRNA-miRNA-mRNA networks. The bioinformatic analyses demonstrated that several abnormal expression circRNAs may contribute to the etiopathogenesis and development of Redondoviridae-related periodontitis. The findings of the present study have enhanced the current understanding of the mechanism of Redondoviridae-related periodontitis process and provide an insight into further applications for diagnostic markers and therapeutic uses.
Project description:Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis
Project description:Gene expressions relate to the pathogenesis of periodontitis and have a crucial role in local tissue destruction and susceptibility to the disease. The aims of the present study were to explore comprehensive gene expressions/transcriptomes in periodontitis-affected gingival tissues, and to identify specific biological processes. The purpose of the present study was 1) to compare comprehensive gene expression/transcriptomes of periodontitis-affected gingival tissues with those of healthy tissues by using microarray and data mining technologies, and 2) to analyze significantly differentially expressed genes which belong to pathological pathways in periodontitis by qRT-PCR. Two distinct gingival samples including healthy and periodontal-affected gingiva were taken from 3 patients with severe chronic periodontitis. Total RNAs from 6 gingival tissue samples were used for microarray and data-mining analyses. Comparisons, gene ontology, and pathway frequency analyses were performed and identified significant biological pathways in periodontitis. Quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR) analyse using 14 chronic periodontitis patients including 3 patients listed above and 14 healthy individuals showed 9 differentially expressed genes in leukocyte migration and cell communication pathways.
Project description:Diabetic nephropathy (DN) is the leading cause of dialysis and is associated with cardiovascular diseases. To prevent the progression of DN, not only glycemic control but also intervention to exacerbating factors such as chronic inflammation and infection. Recent clinical studies have shown the possible association between chronic kidney disease including DN, and periodontitis. However, the causal relationship that periodontitis could contribute to the progression of DN and its molecular mechanisms has not been understood. In the present study, we investigated ligature-induced experimental periodontitis that might exacerbate glomerular pathology in a DN model KK-Ay mice and the underlying molecular mechanisms. KK-Ay mice with experimental periodontitis showed significantly increased urinary albumin to creatinine ratio, and glomerular pathologies such as glomerular size, mesangial expansion area, fibrotic area, and number of CD68-positive leukocytes compared to those without ligatures. RNA-sequencing in the glomeruli revealed that hematopoietic prostaglandin d2 synthase (Hpgds) was the possible factor bridging periodontitis with the progression of DN. We also found that Hpgds expression was significantly upregulated by hyperglycemia and inflammatory stimuli in mesangial cells. Prostaglandin D2 enhanced hyperglycemia-induced collagen expression in mesangial cells and downregulated the tight junction in renal endothelial cells. Lastly, oral administration with an HPGDS inhibitor HQL-79 successfully prevented the progression of DN in KK-Ay mice by experimental periodontitis. Taken together, experimental periodontitis might contribute to the progression of DN via acceleration of glomerular pathology by upregulation of HPGDS in mesangial cells.
Project description:Treatment of periodontitis in people with diabetes remains challenging. Diabetes-enhanced oxidative stress is a primary cause of aggravation of periodontitis. The present study aimed to investigate the therapeutic potential of thioredoxin-1 (TRX1), an essential endogenous antioxidant protein, in the management of periodontitis with diabetes, as well as its role in modulating osteogenic differentiation. Our findings indicated that the production of reactive oxygen species (ROS) was elevated, while the expression of TRX1 was significantly reduced in the periodontal tissues of periodontitis mice with diabetes. Furthermore, knockdown of TRX1 in periodontal ligament stem cells (PDLSCs) resulted in the inhibition of osteogenic differentiation through disrupting Wnt/β-catenin signal pathway. However, this inhibition was restored upon administration of recombinant human TRX1 (rhTRX1). Importantly, rhTRX1 treatment decreased ROS generation, activated Wnt/β-catenin signal pathway and considerably promoted the alveolar bone repair of periodontitis mice with diabetes. These findings highlighted the crucial protective role of TRX1 in periodontitis with diabetes and suggested that it may serve as a potential therapeutic target for refractory periodontitis associated with oxidative stress.