Stimulation by C-type Natriuretic Peptide of the Differentiation of Clonal Osteoblastic MC3T3-E1 Cells

We examined the effects of C-type natriuretic peptide (CNP) and B-type natriuretic peptide receptor (NPR-B) system, which stimulates the intracellular production of cGMP, on osteoblastic differentiation using clonal murine calvarial MC3T3-E1 cells. CNP-like immunoreactivity was detected in the conditioned medium and in lysates of MC3T3-E1 cells. Exposure of cells to CNP caused an increase in the intracellular production of cGMP and the increase was dose-dependent, while ANP had no effect. These results imply that CNP regulates osteoblastic metabolism via NPR-B in an autocrine manner. Northern blot analysis revealed that treatment of MC3T3-E1 cells with CNP increased the steady-state levels of mRNAs for type-I collagen, cellular alkaline phosphatase (ALPase), and osteocalcin, which are well known as markers of osteoblastic differentiation. Our observations suggest the possibility that CNP functions as a local regulator of osteoblastic differentiation, acting via a cGMP-mediated pathway.