Effect Of Wnt/β-catenin Signaling Pathway On GYY4137 Promoting H-BMMSC Osteogenesis

Objective: To investigate the mechanism of GYY4137 depend on Wnt / β-catenin signaling pathway to affect the osteogenic differentiation of h-BMMSC.Methods: Human bone marrow mesenchymal stem cell(h-BMMSC)was cultured using the method of whole-bone-marrow-adherent.The h-BMMSC cultured to the 4th generation were collected and divided into a control group(h-BMMSC),an experimental group(GYY4137 + h-BMMSC),and an inhibition group(GYY4137 +h-BMMSC + DKK1).The cells of each group were cultured until the 12 th day,and the total amount of h-BMMSC RNA was obtained by lysis.RT-PCR was used to detect the expression of target genes(Wnt1、LRP-5、LRP-6)and osteogenesis-related factor genes(Runx-2 、 OSX)in Wnt / β-catenin signaling pathway of each group.To clarify the mechanism of Hnt on the Wnt / β-catenin signaling pathway of h-BMMSC osteogenic differentiation.Then,30 ovariectomized rat models were purchased.Then randomly divided into control group(normal saline),an experimental group(GYY4137),and an inhibitory group(GYY4137 + DKK1).At week 12,rats were sacrificed to obtain femoral specimens,micro-CT scans of femoral bone trabeculae;histopathological observation of HE staining;blood specimens for enzyme-linked immunosorbent assay BALP,PICP,etc.were used to observe bone formation.The static and dynamic parameters of bone were measured by qwinv3-image-analysis-system.Statistical analysis using SPSS25.0 software.Results: The expression levels of target genes and osteogenic related genes measured in the control group and the experimental group were higher than those in the inhibitor group,and there was a significant difference between the groups(P <0.01);the gene expression in the experimental group and the inhibitor group There were also significant differences(P <0.01),and the gene expression in the DKK1 group decreased significantly.Micro-CT scan and HE staining: The bone trabecula of the control group became thinner,the structure was disordered,and the gap increased;the bone trabecula of the experimental group was significantly thickened and showed a reticular structure;the bone trabecula of the control group was still thin and disorderly.Comparison of BALP and PICP test results showed that there was a significant difference between the experimental group and the control group(P <0.01);the difference between theexperimental group and the inhibitor group was significant(P <0.01).Comparing the static and dynamic parameters,the parameter values of the experimental group and the control group were significantly different(P <0.01).The morphological parameters of bone tissue in the experimental group were significantly better than those in the control group(P <0.01),and there was also a significant difference between the experimental group and the inhibitor group(P <0.01).Conclusions: GYY4137 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by regulating the Wnt / β-catenin signaling pathway.