Natriuretic peptides as novel growth factor of growth plate cartilage

Abstract

Recently evidence has accumulated that natriuretic peptides (NPs) are important regulator of endochondral ossification. Three peptides, ANP, BNP and CNP constitute the NPs family. cGMP production through two particulate guanylate cyclases is involved in their signal transduction. ANP and BNP have high affinity for GC-A and CNP for GC-B. Third receptor, called clearance receptor (NPR-C) is involved in NPs clearance. Mice that overexpress BNP or CNP and mice deficient in NPR-C exhibited marked body elongation, whereas mice deficient in CNP showed dwarfism. CNP enhanced longitudinal growth in organ-cultured long bones, and stimulated the differentiation of osteoblast and cartilage lineage cells. Dwarfism was observed in mice deficient in cGMP-dependent protein kinase II which lies downstream to cGMP. Since three genetically body-elongated mice were proven to have mutations in NPR-C, it is possible that CNP/GC-B/cGK II pathway is related to some clinical disorders. CNP is also expected to have therapeutic application to diseases with dwarfism.