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Development. 2017 Oct 1;144(19):3533-3546. doi: 10.1242/dev.155598.

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

Author information

1
Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA.
2
Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
3
Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
4
Center for Clinical & Translational Research, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA.
5
Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA li.zeng@tufts.edu.
6
Department of Orthopedics, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.

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.

KEYWORDS:

Cartilage; Endochondral ossification; Glucose metabolism; Growth plate; IGF2; Postnatal

PMID:
28974642
PMCID:
PMC5665487
DOI:
10.1242/dev.155598
[Indexed for MEDLINE]
Free PMC Article

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