title: Vascular endothelial growth factor gene silencing suppresses wear debris-induced inflammation.
abstract: OBJECTIVE
  Aseptic loosening is the most common complication of total joint replacement, which most likely results from an inflammatory response to wear debris shed from the implant. In this study we aimed to investigate whether the lentivirus-mediated microRNA (miRNA) targeting vascular endothelial growth factor (VEGF) could inhibit wear debris-induced inflammation in a murine model.
  
  
  METHODS
  Titanium alloy particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvarial bone from a syngeneic mouse. After treatment by locally delivered lentivirus-mediated VEGF miRNA, inflammatory tissues were collected for histology and molecular analysis.
  
  
  RESULTS
  We found that (1) locally delivered miRNA inhibited titanium alloy particle-induced tissue inflammation, including the diminished pouch membrane thickness and reduced inflammatory cellular infiltration and that (2) locally delivered miRNA inhibited expressions of the inflammatory cytokines VEGF, tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and receptor activator of nuclear factor kappa B ligand (RANKL).
  
  
  CONCLUSIONS
  These findings suggest that local VEGF inhibition might be a promising therapeutic candidate to alleviate particle-induced inflammation.
authors.affiliation: Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Peng
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Xianlong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000497:Alloys; D000818:Animals; D001862:Bone Resorption; D004195:Disease Models, Animal; D005260:Female; D020868:Gene Silencing; D005822:Genetic Vectors; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics; D010014:Osteolysis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D011475:Prosthesis Failure; D014025:Titanium; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D000497:Alloys; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014025:Titanium