title: Repair effect of coexpression of the hVEGF and hBMP genes via an adeno-associated virus vector in a rabbit model of early steroid-induced avascular necrosis of the femoral head.
abstract: We investigated the repair effect of coexpression of the human vascular endothelial growth factor (hVEGF) and human bone morphogenetic protein (hBMP) genes via an adeno-associated virus (AAV) vector in a rabbit model of early steroid-induced avascular necrosis of the femoral head (SANFH). The following AAV vectors were constructed: AAV-green fluorescent protein, AAV-VEGF, AAV-BMP, and AAV-VEGF/BMP. The rabbit model was induced using lipopolysaccharide and methylprednisolone. Virus vector was injected into the core decompression region at a dose of 25 μL per side after core decompression operation in each group. hVEGF165 and BMP-7 expressions were determined by Western blotting and immunohistochemical staining, and the femoral head was examined by magnetic resonance image scan, histopathologic staining, ink vessel staining, microcomputed tomography scan, and biomechanical assessment to determine the repair effect. The vector AAV-VEGF/BMP successfully expressed hVEGF165 and BMP-7 at the gene and protein levels at 12 weeks after virus injection. The expression of hVEGF165 promoted metabolism of the necrotic region by inducing vessel formation. The expression of BMP-7 promoted osteogenesis by increasing the mineral density and biomechanical strength of the femoral head. The repair effect of the AAV-VEGF/BMP group was better than those of the AAV-VEGF and AAV-BMP groups in the rabbit early SANFH model. The AAV-VEGF/BMP vector improved the bone repair capacity of the necrotic femoral head by inducing angiogenesis and improving bone quality in the femoral head.
authors.affiliation: The First Department of Orthopaedics, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The First Department of Orthopaedics, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Ultrasound, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Medical Imaging Center, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Li
authors.affiliation: The First Department of Orthopaedics, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Dang
authors.affiliation: The First Department of Orthopaedics, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: wkzh1955@163.com.
authors.forename: Kun-Zheng
authors.initials: KZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D015519:Bone Density; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics* / Q000627:therapeutic use; D001861:Bone Regeneration; D019245:Compressive Strength; D000229:Dependovirus / Q000378:metabolism*; D004195:Disease Models, Animal; D005271:Femur Head Necrosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects; D018919:Neovascularization, Physiologic; D011817:Rabbits; D013194:Staining and Labeling; D013256:Steroids / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000627:therapeutic use; D014945:Wound Healing; D055114:X-Ray Microtomography
chemical_list: D055419:Bone Morphogenetic Protein 7; D013256:Steroids; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D008775:Methylprednisolone