Bone homeostasis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat5.
J Clin Invest
; 106(9): 1095-103, 2000 Nov.
Article
em En
| MEDLINE
| ID: mdl-11067862
ABSTRACT
Growth hormone (GH) regulates both bone growth and remodeling, but it is unclear whether these actions are mediated directly by the GH receptor (GHR) and/or IGF-I signaling. The actions of GH are transduced by the Jak/Stat signaling pathway via Stat5, which is thought to regulate IGF-I expression. To determine the respective roles of GHR and IGF-I in bone growth and remodeling, we examined bones of wild-type, GHR knockout (GHR(-/-)), Stat5ab(-/-), and GHR(-/-) mice treated with IGF-I. Reduced bone growth in GHR(-/-) mice, due to a premature reduction in chondrocyte proliferation and cortical bone growth, was detected after 2 weeks of age. Additionally, although trabecular bone volume was unchanged, bone turnover was significantly reduced in GHR(-/-) mice, indicating GH involvement in the high bone-turnover level during growth. IGF-I treatment almost completely rescued all effects of the GHR(-/-) on both bone growth and remodeling, supporting a direct effect of IGF-I on both osteoblasts and chondrocytes. Whereas bone length was reduced in Stat5ab(-/-) mice, there was no reduction in trabecular bone remodeling or growth-plate width as observed in GHR(-/-) mice, indicating that the effects of GH in bone may not involve Stat5 activation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenvolvimento Ósseo
/
Fator de Crescimento Insulin-Like I
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Hormônio do Crescimento
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Remodelação Óssea
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Proteínas do Leite
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2000
Tipo de documento:
Article