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In the intestine, mucins are expressed and secreted by goblet cells and enterocytes in a constitutive manner and in response to secretagogues to form a protective mucus layer. This protective barrier is often lost in inflammatory bowel disease (IBD). Interestingly, extracellular nucleotides, through P2Y receptors, were identified as mucin secretagogues in mucinous epithelia. These nucleotides are found in the intestine's extracellular milieu under basal conditions and in higher concentrations in pathologies such as IBD. It was observed that the mucus layer was affected in P2ry6 knockout mice suffering from dextran sodium sulfate (DSS)‐induced colitis. P2ry6−/− mice were more sensitive to DSS‐induced colitis, resulting in larger ulcers and increased disease activity index. Interestingly, the absence of P2Y6 receptor expression negatively affected the mucus quality, as shown by a reduction in sulfomucin staining and the absence of a dense internal fucosylated mucin layer in P2ry6−/− mice. Hence, we cannot rule out that the absence of P2Y6 receptors in knockout animals could negatively impact mucin secretion. However, we did not measure a reduction in the number of goblet cells, as previously reported. Instead, the results suggest that goblet cells rapidly discharged mucins to compensate for the mucus layer's increased lability, which resulted in empty goblet cells that are less visible to mucin staining. This study's results, along with previous reports, point toward a protective role for the P2Y6 receptor in IBD. [ABSTRACT FROM AUTHOR]

Bone mineralization is an orchestrated process by which mineral crystals are deposited by osteoblasts; however, the detailed mechanisms remain to be elucidated. The presence of P2X7 receptor (P2X7R) in immature and mature bone cells is well established, but contrasting evidence on its role in osteogenic differentiation and deposition of calcified bone matrix remains. To clarify these controversies in the present study, we investigated P2X7R participation in bone maturation. We demonstrated that the P2X7R is expressed and functional in human primary osteoblasts, and identified in the P2RX7 promoter several binding sites for transcription factors involved in bone mineralization. Of particular interest was the finding that P2X7R expression is enhanced by nuclear factor of activated T cells cytoplasmic 1 (NFATc1) overexpression, and accordingly, NFATc1 is recruited at the P2RX7 gene promoter in SaOS2 osteoblastic‐like cells. In conclusion, our data provide further insights into the regulation of P2X7R expression and support the development of drugs targeting this receptor for the therapy of bone diseases. [ABSTRACT FROM AUTHOR]