METHOD OF TREATING SKELETAL DYSPLASIAS USING VESSEL DILATOR

摘要

C-natriuretic peptide (CNP) has been shown to regulate proliferation of mouse and rat osteoblasts. Genetic deletion of CNP results in dwarfism. CNP effects on bone growth involve inhibition of MEK 1 and ERK 1/2 kinases mediated via the intracellular messenger cyclic GMP. Vessel dilator is another natriuretic peptide synthesized by the atrial natriuretic peptide gene whose biologic half-life is 12 times longer than CNP. Vessel dilator's biologic effects on proliferating cells are mediated via inhibiting MEK 1/2 and ERK 1/2 kinases via cyclic GMP. Vessel dilator was not studied previously on osteoblasts. CNP and vessel dilator were tested in dose-response studies enhanced human osteoblasts' proliferation, showing that vessel dilator has identical mechanisms of action to CNP but much longer biologic half-life and effects at lower concentrations. Vessel dilator exhibited therapeutic effect for use in human achondroplasia, short stature and osteoporosis by stimulating osteoblast proliferation.