Background:Zinc-finger E-box-binding homeobox-1(ZEB1)is predominantly found in type-H vessels.However,the roles of ZEB1 and type-H vessels in steroid-i nduced osteonecrosis of the femoral head(SONFH)are unclear.Method...Background:Zinc-finger E-box-binding homeobox-1(ZEB1)is predominantly found in type-H vessels.However,the roles of ZEB1 and type-H vessels in steroid-i nduced osteonecrosis of the femoral head(SONFH)are unclear.Methods:Human femoral heads were collected to detect the expression of ZEB1and the levels of type-H vessels.Then,the SONFH model was developed by injecting C57BL/6 mice with lipopolysaccharide and methylprednisolone.Microcomputed tomography,angiography,double calcein labeling,immunofluorescence,immunohistochemistry,quantitative real-time polymerase chain reaction,and Western blotting were performed to detect the expression of ZEB1,the Wnt/β-catenin pathway,type-H vessels,and the extent to which ZEB1 mediates angiogenesis and osteogenesis.Human umbilical vein endothelial cells were also used to explore the relationship between ZEB1 and the Wnt/β-catenin pathway.Results:We found that ZEB1 expression and the formation of type-H vessels decreased in SONFH patients and in a mouse model.The number of vascular endothelial growth factors in the femoral heads also decreased.Moreover,the bone mineral density,trabecular number,mineral apposition rate,and expression of genes related to osteogenesis decreased.After ZEB1 knockdown,angiogenesis and osteogenesis decreased.However,the numbers of type-H vessels and the extent of angiogenesis and osteogenesis improved after activation of the Wnt/β-catenin pathway.Conclusions:The ZEB1 expression decreased in SONFH,causing a decrease in type-H vessel,and it mediated angiogenesis and osteogenesis by regulating the Wnt/β-catenin pathway,ultimately accelerating the process of SONFH.展开更多
基金China Postdoctoral Science Foundation,Grant/Award Number:2021M692575Fundamental Research Funds for the Central Universities,Grant/Award Number:xzy022024016National Natural Science Foundation of China,Grant/Award Number:82002311。
文摘Background:Zinc-finger E-box-binding homeobox-1(ZEB1)is predominantly found in type-H vessels.However,the roles of ZEB1 and type-H vessels in steroid-i nduced osteonecrosis of the femoral head(SONFH)are unclear.Methods:Human femoral heads were collected to detect the expression of ZEB1and the levels of type-H vessels.Then,the SONFH model was developed by injecting C57BL/6 mice with lipopolysaccharide and methylprednisolone.Microcomputed tomography,angiography,double calcein labeling,immunofluorescence,immunohistochemistry,quantitative real-time polymerase chain reaction,and Western blotting were performed to detect the expression of ZEB1,the Wnt/β-catenin pathway,type-H vessels,and the extent to which ZEB1 mediates angiogenesis and osteogenesis.Human umbilical vein endothelial cells were also used to explore the relationship between ZEB1 and the Wnt/β-catenin pathway.Results:We found that ZEB1 expression and the formation of type-H vessels decreased in SONFH patients and in a mouse model.The number of vascular endothelial growth factors in the femoral heads also decreased.Moreover,the bone mineral density,trabecular number,mineral apposition rate,and expression of genes related to osteogenesis decreased.After ZEB1 knockdown,angiogenesis and osteogenesis decreased.However,the numbers of type-H vessels and the extent of angiogenesis and osteogenesis improved after activation of the Wnt/β-catenin pathway.Conclusions:The ZEB1 expression decreased in SONFH,causing a decrease in type-H vessel,and it mediated angiogenesis and osteogenesis by regulating the Wnt/β-catenin pathway,ultimately accelerating the process of SONFH.
