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Lgr4 promotes aerobic glycolysis and differentiation in osteoblasts via the canonical Wnt/β ‐catenin pathway
Author(s) -
Yang Yuying,
Zhou Yanman,
Xu Jingzun,
Sun Lihao,
Tao Bei,
Wang Weiqing,
Wang Jiqiu,
Zhao Hongyan,
Liu Jianmin
Publication year - 2021
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.4321
Subject(s) - wnt signaling pathway , glycolysis , anaerobic glycolysis , chemistry , osteoblast , endocrinology , dkk1 , bone remodeling , medicine , catenin , microbiology and biotechnology , lrp6 , signal transduction , metabolism , biochemistry , biology , in vitro
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/β‐catenin signaling rescued the glycolytic dysfunction. Lgr4 promotes the expression of pyruvate dehydrogenase kinase 1 (pdk1) and is abolished by interfering canonical Wnt/β‐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. © 2021 American Society for Bone and Mineral Research (ASBMR).