Prostaglandin E2 Enhances B-Type Natriuretic Peptide Receptor Expression in Calvarial Osteoblasts through EP1 Subtype of Prostaglandin E2 Receptor

The B-type natriuretic peptide receptor (NPR-B) is a specific receptor for the C-type natriuretic peptide (CNP) and the binding of the peptide to NPR-B stimulates the bone formation by osteoblasts. However, the mechanism behind the reaulation of NPR-B expression in osteoblasts remains unknown. In this study, we examined the role of prostaglandin E-2 (PGE(2)) through the PGE(2) receptor subtypes, EP1, EP2, EP3 and EP4, in the regulation of NPR-B expression using calvarial osteoblasts from rats of various ages. Reverse Transcription-PCR (RT-PCR) and Western blotting analyses revealed that PGE(2) or 17-phenyl-omega-trinor PGE(2), an EP1 agonist, increased the expression of NPR-B of calvarial osteoblasts from 25-week-old rats in a time- and dose-dependent manner. The PGE(2)- and EP1 agonist-induced increase in NPR-B expression was blocked by treating with SC19220, an EP1 antagonist. By contrast, agonists for EP2, EP3, and EN failed to affect the NPR-B expression. The basal mRNA level of NPR-B and EP1 continuously decreased with the age of cell donors between 10 to 60 weeks and remained constant over 60 weeks. The degree of EP1 agonist-induced increase in NPR-B mRNA level gradually decreased with age of cell donors between 10 to 60 weeks, and no significant effect of EP1 agonist on the NPR-B mRNA level was observed over 60 weeks. From these results, we concluded that PGE, acts as a regulator of NPR-B expression through the EP1 receptor in osteoblasts and age-related decrease in EP1 expression causes a decrease in NPR-B expression.