Method of treating skeletal dysplasias using vessel dilator

Abstract

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.

What is claimed is: 
     
         1 . A method of treating skeletal disorders, comprising administering a therapeutically effective amount of vessel dilator to a patient in need thereof;
 wherein the skeletal disorder is achondroplasia skeletal dysplasia, short stature, osetopenia, osteoporosis, osteomalacia, hypoparathyroidism, tumor associated osteomalacia, rickets, osteogenesis imperfecta, osteitis fibrosa cystic secondary to hyperparathyroidism, Paget's Disease, or osteitis deformans.   
     
     
         2 . The method of  claim 1 , wherein the vessel dilator is administered at a concentration of between 10 pM and 10 nM. 
     
     
         3 . The method of  claim 2 , wherein the vessel dilator is administered at 1 nM. 
     
     
         4 . The method of  claim 2 , wherein the vessel dilator is administered at 100 pM. 
     
     
         5 . The method of  claim 2 , wherein the vessel dilator is administered at 10 pM. 
     
     
         6 . The method of  claim 1 , wherein the vessel dilator is administered at a concentration of between 0.000258 ng/kg to 0.0028 pg/kg of body weight. 
     
     
         7 . The method of  claim 1 , wherein the vessel dilator is administered at a concentration of between 10 pM and 1 nM. 
     
     
         8 . The method of  claim 1 , wherein the vessel dilator is administered 4 times per day. 
     
     
         9 . The method of  claim 8 , wherein the vessel dilator is administered about every 6 hours. 
     
     
         10 . The method of  claim 9 , wherein the vessel dilator is administered every 6 hours. 
     
     
         11 . A method of treating osteoporosis, comprising administering a therapeutically effective amount of vessel dilator to a patient in need thereof. 
     
     
         12 . The method of  claim 11 , wherein the vessel dilator is administered at a concentration of between 10 pM and 10 nM. 
     
     
         13 . The method of  claim 12 , wherein the vessel dilator is administered at 1 nM. 
     
     
         14 . The method of  claim 12 , wherein the vessel dilator is administered at 100 pM. 
     
     
         15 . The method of  claim 12 , wherein the vessel dilator is administered at 10 pM. 
     
     
         16 . The method of  claim 11 , wherein the vessel dilator is administered at a concentration of between 0.000258 ng/kg to 0.0028 pg/kg of body weight. 
     
     
         17 . The method of  claim 11 , wherein the vessel dilator is administered 4 times per day. 
     
     
         18 . The method of  claim 17 , wherein the vessel dilator is administered about every 6 hours. 
     
     
         19 . The method of  claim 18 , wherein the vessel dilator is administered every 6 hours.