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

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          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.

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          Author and article information

          Journal
          Cell
          Cell
          1097-4172
          0092-8674
          Jun 18 2015
          : 161
          : 7
          Affiliations
          [1 ] Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
          [2 ] Department of Medicine and Molecular Pharmacology, The Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
          [3 ] Faculty of Pharmacy, Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.
          [4 ] Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: gk2172@cumc.columbia.edu.
          Article
          S0092-8674(15)00579-6 NIHMS691966
          10.1016/j.cell.2015.05.029
          4475280
          26091038
          Copyright © 2015 Elsevier Inc. All rights reserved.

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