Lgr4 promotes aerobic glycolysis and differentiation in osteoblasts via the canonical Wnt/β‐catenin pathway

ABSTRACT 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 l...

Full description

Saved in:
Bibliographic Details
Published inJournal of bone and mineral research Vol. 36; no. 8; pp. 1605 - 1620
Main Authors Yang, Yu‐ying, Zhou, Yan‐man, Xu, Jing‐zun, Sun, Li‐hao, Tao, Bei, Wang, Wei‐qing, Wang, Ji‐qiu, Zhao, Hong‐yan, Liu, Jian‐min
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.08.2021
Oxford University Press
Subjects
Animals
beta Catenin - metabolism
Bone growth
Bone mass
BONE REMODELING
Catenin
Cell Differentiation
Energy metabolism
GLYCOLYSIS
Lactic acid
Lgr4
Metabolism
Mice
Osteoblastogenesis
OSTEOBLASTS
Osteoblasts - metabolism
Osteogenesis
OSTEOPOROSIS
Pyruvic acid
Receptors, G-Protein-Coupled - genetics
Tumorigenesis
Wnt protein
Wnt Signaling Pathway
GLYCOLYSIS
Lgr4
BONE REMODELING
OSTEOPOROSIS
OSTEOBLASTS
Online AccessGet full text

Cover

More Information
Summary:ABSTRACT 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 (Lgr4osb−/−) exhibit decreased bone mass and strength due to reduced bone formation. Additionally, glycolysis of osteoblasts is impaired in Lgr4osb−/− 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).
Bibliography:Yu‐ying Yang and Yan‐man Zhou contributed equally to this study.
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:0884-0431
1523-4681
1523-4681
DOI:10.1002/jbmr.4321