BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/Stat3 pathway in mesenchymal stem cells

Jie Zhang; Jinhai Jiang; Hang Liu; Shiyu Wang; Kaixin Ke; Siyuan Liu; Yue Jiang; Lu Liu; Xiang Gao; Baicheng He; Yuxi Su

doi:10.1016/j.gendis.2023.101075

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BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/Stat3 pathway in mesenchymal stem cells

Full-length article | 更新时间：2024-02-04

- BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/Stat3 pathway in mesenchymal stem cells
- BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/Stat3 pathway in mesenchymal stem cells
- Genes & Diseases 2024年11卷第3期
- 作者机构：
  
  1. China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Jiangxi Hospital Affiliated Children’s Hospital of Chongqing Medical University,Jiangxi,China,330000
  2. Department of Pharmacology, School of Pharmacy, Chongqing Medical University,Chongqing,China,400016
  3. National Clinical Research Center for Child Health and Disorders,China
  4. Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University,Chongqing,China,400016
  5. Orthopedics Department, Children's Hospital of Chongqing Medical University,Chongqing,China,400014
  6. Department of Orthopedics, Second Affiliated Hospital of Chongqing Medical University,Chongqing,China,400016
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2023.101075
  中图分类号：
- 纸质出版日期：2024，
  
  网络出版日期：2024-5-1，
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Jie Zhang, Jinhai Jiang, Hang Liu, 等. BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/Stat3 pathway in mesenchymal stem cells[J]. Genes & Diseases, 2024,11(3).

Jie Zhang, Jinhai Jiang, Hang Liu, et al. BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/Stat3 pathway in mesenchymal stem cells[J]. Genes & Diseases, 2024,11(3).
Jie Zhang, Jinhai Jiang, Hang Liu, 等. BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/Stat3 pathway in mesenchymal stem cells[J]. Genes & Diseases, 2024,11(3). DOI： 10.1016/j.gendis.2023.101075.

Jie Zhang, Jinhai Jiang, Hang Liu, et al. BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/Stat3 pathway in mesenchymal stem cells[J]. Genes & Diseases, 2024,11(3). DOI： 10.1016/j.gendis.2023.101075.

摘要

Abstract

Bone defects and non-union are prevalent in clinical orthopedy

and the outcomes of current treatments are often suboptimal. Bone tissue engineering offers a promising approach to treating these conditions effectively. Bone morphogenetic protein 9 (BMP9) can commit mesenchymal stem cells to osteogenic lineage

and a knowledge of the underlying mechanisms may help advance the field of bone tissue engineering. Leucine-rich repeats containing G protein-coupled receptor 4 (LGR4)

a member of G protein-coupled receptors

is essential for modulating bone development. This study is aimed at investigating the impact of LGR4 on BMP9-induced osteogenesis in mesenchymal stem cells as well as the underlying mechanisms. Bone marrow stromal cells from

BMP9

-knockout mice exhibited diminished LGR4 expression

and exogenous LGR4 clearly restored the impaired osteogenic potency of the bone marrow stromal cells. Furthermore

LGR4 expression was increased by BMP9 in C3H10T1/2 cells. LGR4 augmented the benefits of BMP9-induced osteogenic markers and bone formation

whereas LGR4 inhibition restricted these effects. Meanwhile

the BMP9-induced lipogenic markers were increased by LGR4 inhibition. The protein levels of Raptor and p-Stat3 were elevated by BMP9. Raptor knockdown or p-Stat3 suppression attenuated the osteoblastic markers and LGR4 expression brought on by BMP9. LGR4 significantly reversed the blocking effect of Raptor knockdown or p-Stat3 suppression on the BMP9-induced osteoblastic markers. Raptor interacts with p-Stat3

and p-Stat3 activates the

LGR4

promoter activity. In conclusion

LGR4 boosts BMP9 osteoblastic potency in mesenchymal stem cells

and BMP9 may up-regulate LGR4 via the mTORC1/Stat3 signal activation.

关键词

Keywords

BMP9LGR4mTORC1Osteogenic differentiationSTAT3

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