Title

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

Document Type

Article

Publication Date

10-2017

Institution/Department

Translational Research, MMCRI

Journal Title

Development (Cambridge, England)

MeSH Headings

Animals, Animals, Newborn, Bone Development, Cartilage, Cell Differentiation, Chondrocytes, Chondrogenesis, Gene Expression Regulation, Developmental, Glucose, Glycolysis, Growth Plate, Hypertrophy, Insulin-Like Growth Factor II, Mice, Models, Biological, Mutation, Organ Culture Techniques, Phenotype

ISSN

1477-9129

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.

First Page

3533

Last Page

3546

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