Project description:Oral diseases have a lifelong impact on human health and quality of life. Down syndrome (DS) individuals contend with decreased saliva production and periodontal disease for unknown reasons. We investigated the molecular mechanisms of hyposalivation in a DS mouse model (Dp16 mice) and identified decreased Ca2+ uptake in salivary glands essential for saliva fluid secretion. Human iPSC from DS individuals also showed decreased Ca2+ uptake. Decreased saliva in Dp16 mice altered the oral and gut microbiome enriched in succinate-associate microbes. Metabolomic analysis confirmed elevated succinate levels, a signaling molecule linked to periodontal disease. Because Ca2+ dysregulation and hyposalivation are features of Sjogren’s disease, we addressed if DS individuals might be at greater risk of developing Sjogren’s by treating Dp16 mice with DMXAA. Treated Dp16 mice exhibited signs of Sjogren’s. Using the therapeutic agent pilocarpine prescribed in the management of Sjogren’s we enhanced salivation and decreased inflammation.
Project description:Saliva is a convenient non-invasive source of liquid biopsy to monitor human health and diagnose diseases. In particular, extracellular vesicles (EVs) in saliva can potentially reveal clinically relevant information for systemic health. Recent studies have shown that RNA in saliva EVs could be exploited as biomarkers for disease diagnosis. However, there is no standardized protocol for profiling RNA in saliva EV nor clear guideline on selecting saliva fractions for biomarker analysis. To address these issues, we established a robust protocol for small RNA profiling from fractionated saliva. With this method, we performed comprehensive small RNA sequencing of four saliva fractions, including cell-free saliva (CFS), EV-depleted saliva (EV-D), exosome (EXO), and microvesicle (MV) from ten healthy volunteers. Methods: To address these issues, we established a robust protocol for small RNA profiling from fractionated saliva. With this method, we performed comprehensive small RNA sequencing of four saliva fractions, including cell-free saliva (CFS), EV-depleted saliva (EV-D), exosome (EXO), and microvesicle (MV) from ten healthy volunteers.