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J Clin Invest ; 104(4): 399-407, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10449432

RESUMEN

Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) bind to and activate the same PTH/PTHrP receptor. Deletion of either the PTHrP gene or the PTH/PTHrP receptor gene leads to acceleration of differentiation of growth plate chondrocytes. To explore further the functional relationships of PTHrP and the PTH/PTHrP receptor, bones of knockout mice were analyzed early in development, and the phenotypes of double-knockout mice were characterized. One early phenotype is shared by both knockouts. Normally, the first chondrocytes to become hypertrophic are located in the centers of long bones; this polarity is greatly diminished in both these knockouts. The PTH/PTHrP receptor-deficient (PTH/PTHrP-R(-/-)) mice exhibited 2 unique phenotypes not shared by the PTHrP(-/-) mice. During intramembranous bone formation in the shafts of long bones, only the PTH/PTHrP-R(-/-) bones exhibit a striking increase in osteoblast number and matrix accumulation. Furthermore, the PTH/PTHrP-R(-/-) mice showed a dramatic decrease in trabecular bone formation in the primary spongiosa and a delay in vascular invasion of the early cartilage model. In the double-homozygous knockout mice, the delay in vascular invasion did not occur. Thus, PTHrP must slow vascular invasion by a mechanism independent of the PTH/PTHrP receptor.


Asunto(s)
Desarrollo Óseo/genética , Desarrollo Óseo/fisiología , Huesos/anomalías , Proteínas/genética , Proteínas/fisiología , Receptores de Hormona Paratiroidea/genética , Receptores de Hormona Paratiroidea/fisiología , Animales , Huesos/irrigación sanguínea , Femenino , Masculino , Ratones , Ratones Noqueados , Osteoblastos/patología , Proteína Relacionada con la Hormona Paratiroidea , Fenotipo , Embarazo , Receptor de Hormona Paratiroídea Tipo 1
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