G-protein-coupled receptors (GPCRs) have emerged as critical regulators of bone development and remodeling. In this study, we aimed to identify specific GPCR mutations in osteoporotic patients via nex Show more
G-protein-coupled receptors (GPCRs) have emerged as critical regulators of bone development and remodeling. In this study, we aimed to identify specific GPCR mutations in osteoporotic patients via next-generation sequencing (NGS). We performed NGS sequencing of six genomic DNA samples taken from osteoporotic patients and two genomic DNA samples from healthy donors. Next, we searched for single-nucleotide polymorphisms (SNPs) in GPCR genes that are associated with osteoporosis. For three osteoporotic patients and one healthy donor, bone biopsies were used to generate patient-specific mesenchymal stem cell (MSC) lines, and their ability to undergo osteodifferentiation was analyzed. We found that MSCs derived from osteoporotic patients have a different response to osteoinductive factors and impaired osteogenic differentiation using qPCR and histochemical staining assays. The NGS analysis revealed specific combinations of SNPs in GPCR genes in these patients, where SNPs in Show less
Obesity, type 2 diabetes and associated metabolic diseases are characterized by low-grade systemic inflammation which involves interplay of nutrition and monocyte/macrophage functions. We suggested th Show more
Obesity, type 2 diabetes and associated metabolic diseases are characterized by low-grade systemic inflammation which involves interplay of nutrition and monocyte/macrophage functions. We suggested that some factors such as nutrient components, neuropeptides involved in the control of gastrointestinal functions, and gastrointestinal hormones might influence immune cell functions and in this way contribute to the disease pathogenesis. The aim of this study was to investigate the mRNA expression of twelve nutrition-associated receptors in peripheral blood mononuclear cells (PBMC), isolated monocytes and monocyte-derived macrophages and their regulation under the switching from the high-carbohydrate low-fat diet to the low-carbohydrate high-fat (LC/HFD) isocaloric diet in healthy humans. The mRNA expression of receptors for short chain fatty acids (GPR41, GPR43), bile acids (TGR5), incretins (GIPR, GLP1R), cholecystokinin (CCKAR), neuropeptides VIP and PACAP (VIPR1, VIPR2), and neurotensin (NTSR1) was detected in PBMC and monocytes, while GPR41, GPR43, GIPR, TGR5, and VIPR1 were found in macrophages. Correlations of the receptor expression in monocytes with a range of metabolic and inflammatory markers were found. In non-obese subjects, the dietary switch to LC/HFD induced the increase of GPR43 and VIPR1 expression in monocytes. No significant differences of receptor expression between normal weight and moderately obese subjects were found. Our study characterized for the first time the expression pattern of nutrition-associated receptors in human blood monocytes and its dietary-induced changes linking metabolic responses to nutrition with immune functions in health and metabolic diseases. Show less