Vessel dilator and C-type natriuretic peptide enhance the proliferation of human osteoblasts

Abstract

C-natriuretic peptide (CNP) has been shown to regulate proliferation of mouse and rat osteoblasts. Genetic deletion of CNP results in dwarfism. Overexposure of CNP has been associated with arachnodactyly of hands and feet with a very long hallux bilaterally in a 14-y-old girl. CNP effects on bone growth involve inhibition of MEK 1 and ERK 1/2 kinases mediated via the intracellular messenger cGMP. 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 cGMP. Vessel dilator has never been studied on osteoblasts. CNP at 10 (nanomolar) nM (p = 0.02) and vessel dilator at 10 nM, 1 nM, 100 (picomolar) pM, and 10 pM (p ≤0.01) in dose-response studies enhanced human osteoblasts' proliferation. This first study of human osteoblasts would suggest that vessel dilator with a much longer biologic half-life and with osteoblast-stimulatory effects at lower concentrations than CNP may have therapeutic potential in human achondroplasia, short stature, and osteoporosis. Vessel dilator stimulates osteoblast proliferation whereas most current therapies of osteoporosis target osteoclasts. © 2010 International Pediatric Research Foundation, Inc.