Journal article
Glucose metabolism induced by Bmp signaling is essential for murine skeletal development
Nature communications, Vol.9(1), pp.4831-11
11/16/2018
DOI: 10.1038/s41467-018-07316-5
PMCID: PMC6240091
PMID: 30446646
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.
Details
- Title: Subtitle
- Glucose metabolism induced by Bmp signaling is essential for murine skeletal development
- Creators
- Seung-Yon Lee - Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USAE Dale Abel - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, USAFanxin Long - The Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, 19104, USA. longf1@email.chop.edu
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.9(1), pp.4831-11
- DOI
- 10.1038/s41467-018-07316-5
- PMID
- 30446646
- PMCID
- PMC6240091
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- England
- Grant note
- R01 AR060456 / NIAMS NIH HHS R01 DK111212 / NIDDK NIH HHS R01 AR055923 / NIAMS NIH HHS
- Language
- English
- Date published
- 11/16/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024502202771
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