Increased glycolysis mediates Wnt7b‐induced bone formation. Issue 7 (26th March 2019)

• Record Type: Journal Article
• Authors: Chen, Hong; Ji, Xing; Lee, Wen-Chih; Shi, Yu; Li, Boer; Abel, Dale; Jiang, Dianming; Huang, Wei; Long, Fanxin
• Is Part Of: FASEB journal. Volume 33:Issue 7(2019)
• Page Start: 7810
• Page End: 7821
• Publication Date: 2019-03-26
• Subjects: Glut1 -- Slc2a1 -- glucose -- osteoblast -- mouse; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201900201RR
• Languages: English
• ISSNs: 0892-6638

Abstract

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. FASEB J. 33, 7810–7821 (2019). www.fasebj.org