title: Wear particles promote reactive oxygen species-mediated inflammation via the nicotinamide adenine dinucleotide phosphate oxidase pathway in macrophages surrounding loosened implants.
abstract: OBJECTIVE
  Prosthesis loosening is closely associated with chronic inflammatory cytokine secretion by macrophages, which are activated by wear particles or inflammatory stimulants such as lipopolysaccharide (LPS). Reactive oxygen species (ROS) are critical regulators of inflammation, but their enzymatic sources in response to wear particles and their effects on peri-implant LPS-tolerance remain unclear.
  
  
  METHODS
  Three ROS-related enzymes-nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1 and -2 and catalase-were investigated in interface membrane tissues and in titanium (Ti) particle-stimulated macrophages in vitro. The generation of ROS and downstream inflammatory effects were measured with or without pre-incubation with apocynin, an NOX inhibitor.
  
  
  RESULTS
  Pre-exposure to Ti particles attenuated NF-κB activation in LPS-stimulated macrophages, indicating that wear particles suppress immune response, which may lead to chronic inflammation. NOX-1 and -2 were highly expressed in aseptically loosened interface membranes and in macrophages stimulated with Ti particles; the particles induced a moderate amount of ROS generation, NF-κB activation, and TNF-α secretion in macrophages, and these effects were suppressed by apocynin.
  
  
  CONCLUSIONS
  Wear particles induce ROS generation through the NOX signaling pathway, resulting in persistent inflammation and delayed loosening. Thus, the suppression of NOX activity may be a useful strategy for preventing prosthesis loosening.
authors: Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors: Weishen
authors: W
authors: Chen
authors: Ziqing
authors: Z
authors: Li
authors: Ying
authors: Y
authors: Guo
authors: Yuhuan
authors: Y
authors: Zhou
authors: Ziji
authors: Z
authors: Zhang
authors: Yangchun
authors: Y
authors: Zhang
authors: Guotian
authors: G
authors: Luo
authors: Xing
authors: X
authors: Yang
authors: Weiming
authors: W
authors: Liao
authors: Chaohong
authors: C
authors: Li
authors: Lingwu
authors: L
authors: Chen
authors: Puyi
authors: P
authors: Sheng
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007249:Inflammation; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010316:Particle Size; D010766:Phosphorylation / Q000187:drug effects; D019736:Prostheses and Implants; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C056165:acetovanillone; D014025:Titanium; D002374:Catalase; D019255:NADPH Oxidases