Mechanism of Osteonectin Promoting Osteogenic Differentiation of Bone Marrow-derived Mesenchymal Stem Cells and Its Correlation with Adoles-cent Idiopathic Scoliosis
Objective To explore the molecular mechanism of Osteonectin(ON)in promoting osteogenic differentia-tion of bone marrow-derived mesenchymal stem cells(BMSCs)and the role of ON in the development of adolescent idiopathic scoliosis(AIS).Methods Twenty AIS patients and 20 healthy subjects who underwent physical examination from May 2020 to May 2022 were enrolled as AIS group and healthy groups respectively.The expression levels of ON,BMP2 and Wnt/β-catenin signaling pathway-related genes(Tcf7,Lef1)and osteogenic differentiation-related genes(Runx2,Osteocalcin)in BMSCs of the two groups were determined by qRT-PCR.The Cobb angle of AIS patients was detected by X-ray,and the corre-lation between the above gene expression levels and the Cobb angle was analyzed.BMSCs were added with ON and BMP2 in-hibitor Noggin,and divided into control group,ON group,and ON + Noggin group.The expression levels of BMP2,Tcf7,Lef1,Runx2 and Osteocalcin mRNA in BMSCs were detected by qRT-PCR.The enrichment level of β-catenin in Runx2 and Osteocalcin gene transcription start sites(TSS)was detected by ChIP-qPCR.Results Compared with healthy group,the ex-pression levels of ON,BMP2,Tcf7,Lef1,Runx2 and Osteocalcin mRNA in BMSCs in AIS group were decreased(P<0.05).The expression levels of ON,BMP2,Tcf7,Lef1,Runx2 and Osteocalcin were negatively correlated with the Cobb an-gle in AIS patients(r =-0.466 3,-0.369 1,-0.272 7,-0.543 4,-0.606 5,-0.343 3,P<0.05,P<0.01).Compared with the control group,the expression levels of BMP2,Tcf7,Lef1,Runx2 and Osteocalcin mRNA in BMSCs in ON group were increased,and the TSS enrichment levels of Runx2 and Osteocalcin mRNA in β-catenin group were increased(P<0.05).Compared with the ON group,the expression levels of Tcf7,Lef1,Runx2 and Osteocalcin genes in BMSCs in the ON +Noggin group were decreased,and the TSS enrichment level of β-catenin in Runx2 and Osteocalcin genes was also decreased(P<0.05).Conclusion In AIS patients,the expression of ON,BMP2-Wnt/β-catenin in BMSCs,and the level of osteogenic differentiation are negatively correlated with the development of AIS disease.Osteonectin enables β-catenin to transcriptionally activate osteogenic differentiation-related genes by activating the BMP2-Wnt/β-catenin signaling pathway,thereby promoting the osteogenic differentiation of BMSCs.
万方数据
维普
