Natriuretic peptide regulation of endochondral ossification. Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway.
The natriuretic peptide family consists of three structurally related endogenous ligands: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The biological actions of natriuretic peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The natriuretic peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-peptide GC-coupled natriuretic peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias. This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.
Yasoda
A
A
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan.
Ogawa
Y
Y
Suda
M
M
Tamura
N
N
Mori
K
K
Sakuma
Y
Y
Chusho
H
H
Shiota
K
K
Tanaka
K
K
Nakao
K
K
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D001846:Bone Development; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression; D006162:Guanylate Cyclase / Q000235:genetics; D051379:Mice; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009924:Organ Culture Techniques; D010012:Osteogenesis; D010446:Peptide Fragments / Q000494:pharmacology; D011506:Proteins / Q000502:physiology*; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics; D013977:Tibia / Q000196:embryology
D010446:Peptide Fragments; D011506:Proteins; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C