Increased glycolysis mediates Wnt7b-induced bone formation
Increased glycolysis mediates Wnt7b-induced bone formation
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DOI：
10.1096/fj.201900201rr
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发表时间：
2019-07-01
期刊：
影响因子：
4.8
通讯作者：
Long, Fanxin
中科院分区：
文献类型：
--
作者：
Chen, Hong;Ji, Xing;Long, Fanxin
无翼/整合（Wnt）信号传导已成为促进骨形成的主要机制和开发抗骨质疏松症的骨合成代谢药物的靶向途径。然而，介导Wnt蛋白潜在治疗作用的下游事件尚未完全了解。以前的研究表明，糖酵解增加与成骨细胞分化响应Wnt信号，但直接的遗传证据葡萄糖代谢的重要性Wnt诱导的骨形成是缺乏。在这里，我们已经产生了复合转基因小鼠过度表达Wnt家族成员7 B（Wnt 7 b）瞬时在成骨细胞谱系的出生后的小鼠，有或没有同时删除的葡萄糖转运蛋白1（Glut 1），也被称为溶质载体家族2，促进葡萄糖转运蛋白成员1。Wnt 7 b在1个月大的小鼠1周的过度表达显着刺激骨形成，但效果基本上被取消没有Glut 1，即使短暂的Glut 1本身的缺失并不影响正常的骨积累。与体内结果一致，Wnt 7 b增加了成骨细胞系原代培养物中Glut 1的表达和葡萄糖消耗，而Glut 1的缺失减少了体外成骨细胞的分化。因此，Wnt 7 b部分通过刺激成骨细胞谱系细胞中的葡萄糖代谢来促进骨形成。陈洪，吉，X.，李，W.- C.的方法，施，Y.，Li，B.，阿贝尔，E. D、江，D.，黄伟，朗角，加-地糖酵解增加介导Wnt 7 b诱导的骨形成。
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.