In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 7 ( 2001-03-27), p. 4016-4021
Abstract:
Longitudinal bone growth is determined by endochondral ossification
that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement.
The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic
peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological
significance of CNP in vivo , we generated mice with
targeted disruption of CNP ( Nppc −/− mice).
The Nppc −/− mice show severe dwarfism as a
result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal
development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic
form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc −/− mice and allow their prolonged
survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and
suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.071389098
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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