Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation

Jianwen Wei, Junko Shimazu, Munevver P. Makinistoglu, Antonio Maurizi, Daisuke Kajimura, Haihong Zong, Takeshi Takarada, Takashi Lezaki, Jeffrey E. Pessin, Eiichi Hinoi, Gerard Karsenty

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

The synthesis of type I collagen, the main component of bone matrix, precedes the expression of Runx2, the earliest determinant of osteoblast differentiation. We hypothesized that the energetic needs of osteoblasts might explain this apparent paradox. We show here that glucose, the main nutrient of osteoblasts, is transported in these cells through Glut1, whose expression precedes that of Runx2. Glucose uptake favors osteoblast differentiation by suppressing the AMPK-dependent proteasomal degradation of Runx2 and promotes bone formation by inhibiting another function of AMPK. While RUNX2 cannot induce osteoblast differentiation when glucose uptake is compromised, raising blood glucose levels restores collagen synthesis in Runx2-null osteoblasts and initiates bone formation in Runx2-deficient embryos. Moreover, RUNX2 favors Glut1 expression, and this feedforward regulation between RUNX2 and Glut1 determines the onset of osteoblast differentiation during development and the extent of bone formation throughout life. These results reveal an unexpected intricacy between bone and glucose metabolism.

Original languageEnglish
Pages (from-to)1576-1591
Number of pages16
JournalCell
Volume161
Issue number7
DOIs
Publication statusPublished - Jun 20 2015
Externally publishedYes

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Osteoblasts
Osteogenesis
Bone
Glucose
AMP-Activated Protein Kinases
Bone Matrix
Collagen Type I
Metabolism
Nutrients
Blood Glucose
Collagen
Embryonic Structures
Bone and Bones
Food
Degradation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Wei, J., Shimazu, J., Makinistoglu, M. P., Maurizi, A., Kajimura, D., Zong, H., ... Karsenty, G. (2015). Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation. Cell, 161(7), 1576-1591. https://doi.org/10.1016/j.cell.2015.05.029

Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation. / Wei, Jianwen; Shimazu, Junko; Makinistoglu, Munevver P.; Maurizi, Antonio; Kajimura, Daisuke; Zong, Haihong; Takarada, Takeshi; Lezaki, Takashi; Pessin, Jeffrey E.; Hinoi, Eiichi; Karsenty, Gerard.

In: Cell, Vol. 161, No. 7, 20.06.2015, p. 1576-1591.

Research output: Contribution to journalArticle

Wei, J, Shimazu, J, Makinistoglu, MP, Maurizi, A, Kajimura, D, Zong, H, Takarada, T, Lezaki, T, Pessin, JE, Hinoi, E & Karsenty, G 2015, 'Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation', Cell, vol. 161, no. 7, pp. 1576-1591. https://doi.org/10.1016/j.cell.2015.05.029
Wei J, Shimazu J, Makinistoglu MP, Maurizi A, Kajimura D, Zong H et al. Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation. Cell. 2015 Jun 20;161(7):1576-1591. https://doi.org/10.1016/j.cell.2015.05.029
Wei, Jianwen ; Shimazu, Junko ; Makinistoglu, Munevver P. ; Maurizi, Antonio ; Kajimura, Daisuke ; Zong, Haihong ; Takarada, Takeshi ; Lezaki, Takashi ; Pessin, Jeffrey E. ; Hinoi, Eiichi ; Karsenty, Gerard. / Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation. In: Cell. 2015 ; Vol. 161, No. 7. pp. 1576-1591.
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