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Glucose metabolism induced by Bmp signaling is essential for murine skeletal development

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  • Seung-Yon Lee

    (Washington University School of Medicine)

  • E. Dale Abel

    (University of Iowa)

  • Fanxin Long

    (Washington University School of Medicine
    Washington University School of Medicine
    The Children’s Hospital of Philadelphia and University of Pennsylvania)

Abstract

Much of the mammalian skeleton originates from a cartilage template eventually replaced by bone via endochondral ossification. Despite much knowledge about growth factors and nuclear proteins in skeletal development, little is understood about the role of metabolic regulation. Here we report that genetic deletion of the glucose transporter Glut1 (Slc2a1), either before or after the onset of chondrogenesis in the limb, severely impairs chondrocyte proliferation and hypertrophy, resulting in dramatic shortening of the limbs. The cartilage defects are reminiscent to those caused by deficiency in Bmp signaling. Importantly, deletion of Bmpr1a in chondrocytes markedly reduces Glut1 levels in vivo, whereas recombinant BMP2 increases Glut1 mRNA and protein levels, boosting glucose metabolism in primary chondrocytes. Biochemical studies identify a Bmp-mTORC1-Hif1a signaling cascade resulting in upregulation of Glut1 in chondrocytes. The results therefore uncover a hitherto unknown connection between Bmp signaling and glucose metabolism in the regulation of cartilage development.

Suggested Citation

  • Seung-Yon Lee & E. Dale Abel & Fanxin Long, 2018. "Glucose metabolism induced by Bmp signaling is essential for murine skeletal development," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07316-5
    DOI: 10.1038/s41467-018-07316-5
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    Cited by:

    1. Aaron Warren & Ryan M. Porter & Olivia Reyes-Castro & Md Mohsin Ali & Adriana Marques-Carvalho & Ha-Neui Kim & Landon B. Gatrell & Ernestina Schipani & Intawat Nookaew & Charles A. O’Brien & Roy Morel, 2023. "The NAD salvage pathway in mesenchymal cells is indispensable for skeletal development in mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Chujiao Lin & Qiyuan Yang & Dongsheng Guo & Jun Xie & Yeon-Suk Yang & Sachin Chaugule & Ngoc DeSouza & Won-Taek Oh & Rui Li & Zhihao Chen & Aijaz A. John & Qiang Qiu & Lihua Julie Zhu & Matthew B. Gre, 2022. "Impaired mitochondrial oxidative metabolism in skeletal progenitor cells leads to musculoskeletal disintegration," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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