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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\/\u03b2-catenin signaling rescued the glycolytic dysfunction. Lgr4 promotes the expression of pyruvate dehydrogenase kinase 1 (pdk1) and is abolished by interfering canonical Wnt\/\u03b2-catenin signaling. Mice lacking Lgr4 specifically in osteoblasts (Lgr4osb\u2212\/\u2212) exhibit decreased bone mass and strength due to reduced bone formation. Additionally, glycolysis of osteoblasts is impaired in Lgr4osb\u2212\/\u2212 mice. Our study reveals a novel function of Lgr4 in regulating the cellular metabolism of osteoblasts. \u00a9 2021 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4321","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T18:53:38Z","timestamp":1620240818000},"page":"1605-1620","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Lgr4 promotes aerobic glycolysis and differentiation in osteoblasts via the canonical Wnt\/\u03b2-catenin pathway"],"prefix":"10.1093","volume":"36","author":[{"given":"Yu-ying","family":"Yang","sequence":"first","affiliation":[{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 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