Regulation of Osteoblast Metabolism by Wnt Signaling.
Regulation of Osteoblast Metabolism by Wnt Signaling.
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DOI：
10.3803/enm.2018.33.3.318
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Riddle RC
中科院分区：
文献类型：
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作者：
Moorer MC;Riddle RC
Wnt/β-连环蛋白信号在达到峰值骨量中起着关键作用，影响间充质祖细胞对成骨细胞谱系的承诺以及成骨细胞沉积骨基质的合成代谢能力。最近的研究表明，这种进化上保守的发育途径部分通过协调成骨细胞活性与中间代谢来发挥其合成代谢作用。这些发现与从糖尿病易感位点克隆编码低密度脂蛋白相关受体 5 (LRP5) Wnt 共受体的基因以及目前已确立的 Wnt 信号传导和代谢之间的联系相一致。在本文中，我们概述了 Wnt 信号在全身代谢中的作用，并回顾了有关 Wnt 信号对成骨细胞利用三种不同能量来源（脂肪酸、葡萄糖和谷氨酰胺）影响的文献。特别关注养分利用的净效应和 Wnt 信号传导的调节模式。机制研究表明，每种底物的利用均受到独特的控制机制的控制，β-连环蛋白依赖性信号传导调节脂肪酸 β-氧化，而葡萄糖和谷氨酰胺的利用不依赖于 β-连环蛋白，并且分别位于哺乳动物雷帕霉素靶点复合物 2 (mTORC2) 和哺乳动物雷帕霉素靶点复合物 1 (mTORC1) 激活的下游。这些数据的出现为 Wnt 信号传导影响骨骼发育的机制提供了新的背景。
Wnt/β-catenin signaling plays a critical role in the achievement of peak bone mass, affecting the commitment of mesenchymal progenitors to the osteoblast lineage and the anabolic capacity of osteoblasts depositing bone matrix. Recent studies suggest that this evolutionarily-conserved, developmental pathway exerts its anabolic effects in part by coordinating osteoblast activity with intermediary metabolism. These findings are compatible with the cloning of the gene encoding the low-density lipoprotein related receptor-5 (LRP5) Wnt co-receptor from a diabetes-susceptibility locus and the now well-established linkage between Wnt signaling and metabolism. In this article, we provide an overview of the role of Wnt signaling in whole-body metabolism and review the literature regarding the impact of Wnt signaling on the osteoblast's utilization of three different energy sources: fatty acids, glucose, and glutamine. Special attention is devoted to the net effect of nutrient utilization and the mode of regulation by Wnt signaling. Mechanistic studies indicate that the utilization of each substrate is governed by a unique mechanism of control with β-catenin-dependent signaling regulating fatty acid β-oxidation, while glucose and glutamine utilization are β-catenin-independent and downstream of mammalian target of rapamycin complex 2 (mTORC2) and mammalian target of rapamycin complex 1 (mTORC1) activation, respectively. The emergence of these data has provided a new context for the mechanisms by which Wnt signaling influences bone development.