LGR6 promotes osteogenesis by activating the Wnt/β-catenin signaling pathway
LGR6 promotes osteogenesis by activating the Wnt/β-catenin signaling pathway
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LGR6 通过激活 Wnt/β-catenin 信号通路促进成骨。
DOI：
10.1016/j.bbrc.2019.08.122
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发表时间：
2019-10-29
影响因子：
3.1
通讯作者：
Chen, Jing
中科院分区：
文献类型：
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作者：
Liu, Sheng-Li;Zhou, Yan-Man;Chen, Jing
富含亮氨酸重复序列的 G 蛋白偶联受体 6 (LGR6) 是视紫红质样 7 跨膜结构域受体超家族的成员，与 LGR4 和 LGR5 具有高度同源性。 LGR6 在成骨祖细胞中高表达，LGR6 缺陷的小鼠表现出指甲和骨再生缺陷。然而，LGR6对成骨祖细胞成骨分化的影响及其潜在机制尚不清楚。本研究利用慢病毒在前成骨细胞MC3T3-E1中过表达并敲低LGR6，观察LGR6对成骨分化的影响，并探讨其可能的分子机制。 LGR6 过表达通过稳定 β-catenin 来增强 MC3T3-E1 细胞中的 Wnt/β-catenin 信号通路，从而促进成骨分化和矿化。相反，LGR6敲低通过增强β-连环蛋白降解从而使Wnt/β-连环蛋白信号通路失活来抑制成骨分化和矿化。这些结果表明，LGR6在成骨祖细胞中高表达，并通过增强β-连环蛋白稳定性以加强Wnt信号通路来促进成骨。该研究为成骨分化的确切机制提供了重要参考。 (C) 2019 年由爱思唯尔公司出版
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 beta-catenin to potentiate the Wnt/beta-catenin signaling pathway in MC3T3-E1 cells. Conversely, LGR6 knockdown inhibited osteogenic differentiation and mineralization by enhancing beta-catenin degradation to inactivate the Wnt/beta-catenin signaling pathway. These results reveal that LGR6 is highly expressed in osteoblastic progenitors, and promotes osteogenesis by enhancing beta-catenin stability to strengthen the Wnt signaling pathway. This study provides an important reference into the exact mechanisms of osteogenic differentiation. (C) 2019 Published by Elsevier Inc.