LGR6 promotes osteogenesis by activating the Wnt/β-catenin signaling pathway

Sheng-Li Liu; Yan-Man Zhou; Da-Bin Tang; Neng Zhou; Wei-Wei Zheng; Zhong-Hua Tang; Cai-Wen Duan; Liang Zheng; Jing Chen

doi:10.1016/j.bbrc.2019.08.122

LGR6 promotes osteogenesis by activating the Wnt/β-catenin signaling pathway

Biochem Biophys Res Commun. 2019 Oct 29;519(1):1-7. doi: 10.1016/j.bbrc.2019.08.122. Epub 2019 Sep 6.

Authors

Sheng-Li Liu¹, Yan-Man Zhou², Da-Bin Tang¹, Neng Zhou¹, Wei-Wei Zheng¹, Zhong-Hua Tang¹, Cai-Wen Duan¹, Liang Zheng³, Jing Chen⁴

Affiliations

¹ Key Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
² Department of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
³ Key Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China. Electronic address: zhengliang@scmc.com.cn.
⁴ Key Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China. Electronic address: chenjing@scmc.com.cn.

PMID: 31500806
DOI: 10.1016/j.bbrc.2019.08.122

Abstract

Leucine-rich repeat containing G-protein-coupled receptor 6 (LGR6) is a member of the rhodopsin-like 7-transmembrane domain receptor superfamily and has high homology to LGR4 and LGR5. LGR6 is highly expressed in osteoblastic progenitors, and LGR6-deficient mice show nail and bone regeneration defect. However, the effect of LGR6 on the osteogenic differentiation of osteoblastic progenitors and its underlying mechanisms are largely unknown. In this study, we overexpressed and knockdown LGR6 with lentivirus in the preosteoblastic cell MC3T3-E1 to observe the effect of LGR6 on osteogenic differentiation and explore its possible molecular mechanism. LGR6 overexpression promoted osteogenic differentiation and mineralization by stabilizing β-catenin to potentiate the Wnt/β-catenin signaling pathway in MC3T3-E1 cells. Conversely, LGR6 knockdown inhibited osteogenic differentiation and mineralization by enhancing β-catenin degradation to inactivate the Wnt/β-catenin signaling pathway. These results reveal that LGR6 is highly expressed in osteoblastic progenitors, and promotes osteogenesis by enhancing β-catenin stability to strengthen the Wnt signaling pathway. This study provides an important reference into the exact mechanisms of osteogenic differentiation.

Keywords: LGR6; Osteoblast; Osteogenesis; Osteoporosis; β-catenin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcification, Physiologic
Cell Differentiation
Cell Line
Gene Knockdown Techniques
Mice
Osteogenesis*
Protein Stability
Proteolysis
Receptors, G-Protein-Coupled / metabolism*
Wnt Signaling Pathway*
beta Catenin / metabolism

Substances

Lgr6 protein, mouse
Receptors, G-Protein-Coupled
beta Catenin