Stimulatory effects of insulin-like growth factor-I on growth plate chondrogenesis are mediated by nuclear factor-kappaB p65.
J Biol Chem
; 283(49): 34037-44, 2008 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-18922796
ABSTRACT
Insulin-like growth factor-I (IGF-I) is an important regulator of endochondral ossification. However, little is known about the signaling pathways activated by IGF-I in growth plate chondrocytes. We have previously shown that NF-kappaB-p65 facilitates growth plate chondrogenesis. In this study, we first cultured rat metatarsal bones with IGF-I and/or pyrrolidine dithiocarbamate (PDTC), a known NF-kappaB inhibitor. The IGF-I-mediated stimulation of metatarsal growth and growth plate chondrogenesis was neutralized by PDTC. In rat growth plate chondrocytes, IGF-I induced NF-kappaB-p65 nuclear translocation. The inhibition of NF-kappaB-p65 expression and activity (by p65 short interfering RNA and PDTC, respectively) in chondrocytes reversed the IGF-I-mediated induction of cell proliferation and differentiation and the IGF-I-mediated prevention of cell apoptosis. Moreover, the inhibition of the phosphatidylinositol 3-kinase and Akt abolished the effects of IGF-I on NF-kappaB activation. In conclusion, our findings indicate that IGF-I stimulates growth plate chondrogenesis by activating NF-kappaB-p65 in chondrocytes.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Insulin-Like I
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Condrogênese
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Fator de Transcrição RelA
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Lâmina de Crescimento
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos