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.