Details

Autor(en) / Beteiligte

• Uchimura, Tomoya
• Hollander, Judith M
• Nakamura, Daisy S
• Liu, Zhiyi
• Rosen, Clifford J
• Georgakoudi, Irene
• Zeng, Li

Titel

An essential role for IGF2 in cartilage development and glucose metabolism during postnatal long bone growth

Ist Teil von

• Development (Cambridge), 2017-10, Vol.144 (19), p.3533-3546

Ort / Verlag

England: The Company of Biologists Ltd

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 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 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 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.