title: Combined VEGF and LMP-1 delivery enhances osteoprogenitor cell differentiation and ectopic bone formation.
abstract: A novel strategy to enhance bone repair is to combine angiogenic factors and osteogenic factors. We combined vascular endothelial growth factor (VEGF) and LIM mineralization protein-1 (LMP-1) by using an internal ribosome entry site to link the genes within a single plasmid. We then evaluated the effects on osteoblastic differentiation in vitro and ectopic bone formation in vivo with a subcutaneously placed PLAGA scaffold loaded with a cloned mouse osteoprogenitor cell line, D1, transfected with plasmids containing VEGF and LMP-1 genes. The cells expressing both genes elevated mRNA expression of RunX2 and β-catenin and alkaline phosphatase activity compared to cells from other groups. In vivo, X-ray and micro-CT analysis of the retrieved implants revealed more ectopic bone formation at 2 and 3 weeks but not at 4 weeks compared to other groups. The results indicate that the combination of the therapeutic growth factors potentiates cell differentiation and may promote osteogenesis.
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine Charlottesville, University of Virginia, Charlottesville, VA 22908, USA. xlwchina@yahoo.com.cn
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wang
authors.forename: Fuai
authors.initials: F
authors.lastname: Cui
authors.forename: Vedavathi
authors.initials: V
authors.lastname: Madhu
authors.forename: Abhijit S
authors.initials: AS
authors.lastname: Dighe
authors.forename: Gary
authors.initials: G
authors.lastname: Balian
authors.forename: Quanjun
authors.initials: Q
authors.lastname: Cui
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D060588:LIM Domain Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis; D010957:Plasmids / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D042442:Vascular Endothelial Growth Factors / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C484381:Pdlim7 protein, mouse; D012333:RNA, Messenger; C493716:Runx2 protein, mouse; D042442:Vascular Endothelial Growth Factors; D051176:beta Catenin; D000469:Alkaline Phosphatase