Increased glycolysis mediates Wnt7b-induced bone formation

Research output: Contribution to journalArticle

Authors

  • Hong Chen
  • Xing Ji
  • Wen Chih Lee
  • Yu Shi
  • Boer Li
  • E. Dale Abel
  • Dianming Jiang
  • Wei Huang
  • Fanxin Long

External Institution(s)

  • Chongqing University of Medical Sciences
  • Washington University St. Louis

Details

Original languageEnglish (US)
Pages (from-to)7810-7821
Number of pages12
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number7
StatusPublished - Jul 1 2019
Peer-reviewedYes

Abstract

Wingless/integrated (Wnt) signaling has emerged as a major mechanism for promoting bone formation and a target pathway for developing bone anabolic agents against osteoporosis. However, the downstream events mediating the potential therapeutic effect of Wnt proteins are not fully understood. Previous studies have indicated that increased glycolysis is associated with osteoblast differentiation in response to Wnt signaling, but direct genetic evidence for the importance of glucose metabolism in Wnt-induced bone formation is lacking. Here, we have generated compound transgenic mice to overexpress Wnt family member 7B (Wnt7b) transiently in the osteoblast lineage of postnatal mice, with or without concurrent deletion of the glucose transporter 1 (Glut1), also known as solute carrier family 2, facilitated glucose transporter member 1. Overexpression of Wnt7b in 1-mo-old mice for 1 wk markedly stimulated bone formation, but the effect was essentially abolished without Glut1, even though transient deletion of Glut1 itself did not affect normal bone accrual. Consistent with the in vivo results, Wnt7b increased Glut1 expression and glucose consumption in the primary culture of osteoblast lineage cells, and deletion of Glut1 diminished osteoblast differentiation in vitro. Thus, Wnt7b promotes bone formation in part through stimulating glucose metabolism in osteoblast lineage cells.-Chen, H., Ji, X., Lee, W.-C., Shi, Y., Li, B., Abel, E. D., Jiang, D., Huang, W., Long, F. Increased glycolysis mediates Wnt7b-induced bone formation.

    Research areas

  • glucose, Glut1, mouse, osteoblast, Slc2a1

Citation formats

APA

Chen, H., Ji, X., Lee, W. C., Shi, Y., Li, B., Abel, E. D., ... Long, F. (2019). Increased glycolysis mediates Wnt7b-induced bone formation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(7), 7810-7821. https://doi.org/10.1096/fj.201900201RR

Harvard

Chen, H, Ji, X, Lee, WC, Shi, Y, Li, B, Abel, ED, Jiang, D, Huang, W & Long, F 2019, 'Increased glycolysis mediates Wnt7b-induced bone formation', FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 33, no. 7, pp. 7810-7821. https://doi.org/10.1096/fj.201900201RR