Glucose metabolism induced by Bmp signaling is essential for murine skeletal development. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Lee, Seung-Yon; Abel, E.; Long, Fanxin
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 11
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-07316-5
• Languages: English
• ISSNs: 2041-1723

Abstract

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. It is unclear how metabolic regulation affects development of the skeleton. Here, the authors show that deletion of the glucose transporterGlut1 (Slc2a1 ) both prior to and following chondrogenesis in the mouse limb impairs chondrocyte proliferation and shortening of the limbs, modulated by BMP signaling.