An essential role for IGF2 in cartilage development and glucose metabolism during postnatal long bone growth.
Development
; 144(19): 3533-3546, 2017 10 01.
Article
em En
| MEDLINE
| ID: mdl-28974642
ABSTRACT
Postnatal bone growth involves a dramatic increase in length and girth. Intriguingly, this period of growth is independent of growth hormone and the underlying mechanism is poorly understood. Recently, an IGF2 mutation was identified in humans with early postnatal growth restriction. Here, we show that IGF2 is essential for longitudinal and appositional murine postnatal bone development, which involves proper timing of chondrocyte maturation and perichondrial cell differentiation and survival. Importantly, the Igf2 null mouse model does not represent a simple delay of growth but instead uncoordinated growth plate development. Furthermore, biochemical and two-photon imaging analyses identified elevated and imbalanced glucose metabolism in the Igf2 null mouse. Attenuation of glycolysis rescued the mutant phenotype of premature cartilage maturation, thereby indicating that IGF2 controls bone growth by regulating glucose metabolism in chondrocytes. This work links glucose metabolism with cartilage development and provides insight into the fundamental understanding of human growth abnormalities.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenvolvimento Ósseo
/
Fator de Crescimento Insulin-Like II
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Cartilagem
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Condrogênese
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Glucose
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Development
Assunto da revista:
BIOLOGIA
/
EMBRIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos