Lgr4 promotes aerobic glycolysis and differentiation in osteoblasts via the canonical Wnt/β-catenin pathway
Lgr4 promotes aerobic glycolysis and differentiation in osteoblasts via the canonical Wnt/β-catenin pathway
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DOI：
10.1002/jbmr.4321
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发表时间：
2021-05-17
影响因子：
6.2
通讯作者：
Liu, Jian-min
中科院分区：
文献类型：
--
作者：
Yang, Yu-ying;Zhou, Yan-man;Liu, Jian-min
Lgr4是一种g蛋白偶联受体，与多种生理和病理过程相关，包括肿瘤发生、能量代谢和骨重塑。然而，Lgr4是否参与成骨细胞的代谢尚不清楚。本研究发现，在成骨前细胞系中，缺乏Lgr4会导致成骨功能下降，同时在氧气充足的情况下，葡萄糖消耗、葡萄糖摄取和乳酸生成也会减少，这被称为有氧糖酵解。激活典型Wnt/ β -连环蛋白信号可挽救糖酵解功能障碍。Lgr4促进丙酮酸脱氢酶激酶1 （pdk1）的表达，并通过干扰典型Wnt/ β -连环蛋白信号通路而被消除。成骨细胞中特异性缺乏Lgr4（Lgr4(osb-/-)）的小鼠由于骨形成减少而表现出骨量和强度下降。此外，Lgr4（osb-/-）小鼠成骨细胞糖酵解功能受损。我们的研究揭示了Lgr4在调节成骨细胞细胞代谢中的新功能。(c) 2021年美国骨与矿物研究学会（ASBMR）。
Lgr4, a G-protein-coupled receptor, is associated with various physiological and pathological processes including oncogenesis, energy metabolism, and bone remodeling. However, whether Lgr4 is involved in osteoblasts' metabolism is not clear. Here we uncover that in preosteoblast cell line, lacking Lgr4 results in decreased osteogenic function along with reduced glucose consumption, glucose uptake, and lactate production in the presence of abundant oxygen, which is referred to as aerobic glycolysis. Activating canonical Wnt/beta-catenin signaling rescued the glycolytic dysfunction. Lgr4 promotes the expression of pyruvate dehydrogenase kinase 1 (pdk1) and is abolished by interfering canonical Wnt/beta-catenin signaling. Mice lacking Lgr4 specifically in osteoblasts (Lgr4(osb-/-)) exhibit decreased bone mass and strength due to reduced bone formation. Additionally, glycolysis of osteoblasts is impaired in Lgr4(osb-/-) mice. Our study reveals a novel function of Lgr4 in regulating the cellular metabolism of osteoblasts. (c) 2021 American Society for Bone and Mineral Research (ASBMR).