title: Periarticular bone loss in antigen-induced arthritis.
abstract: OBJECTIVE
  Bone loss in arthritis is a complex process characterized by bone erosions and periarticular and generalized bone loss. The antigen-induced arthritis (AIA) model is mainly used to study synovitis and joint destruction, including bone erosions; however, periarticular bone loss has been less extensively investigated. The objectives of this study were to characterize and establish AIA as a model for periarticular bone loss, and to determine the importance of NADPH oxidase 2 (NOX-2)-derived reactive oxygen species (ROS) in periarticular bone loss.
  
  
  METHODS
  Arthritis was induced in mice by local injection of antigen in one knee; the other knee was used as a nonarthritis control. At study termination, the knees were collected for histologic assessment. Periarticular bone mineral density (BMD) was investigated by peripheral quantitative computed tomography. Flow cytometric analyses were performed using synovial and bone marrow cells.
  
  
  RESULTS
  AIA resulted in decreased periarticular trabecular BMD and increased frequencies of preosteoclasts, neutrophils, and monocytes in the arthritic synovial tissue. Arthritis induction resulted in an increased capability to produce ROS. However, induction of arthritis in Ncf1 / mice, which lack NOX-2-derived ROS, and control mice resulted in similar reductions in periarticular trabecular BMD.
  
  
  CONCLUSIONS
  The initiation of AIA resulted in periarticular bone loss associated with local effects on inflammatory cells and osteoclasts. Furthermore, based on our observations using this model, we conclude that NOX-2-derived ROS production is not essential for inflammation-mediated periarticular bone loss. Thus, AIA can be used as a model to investigate the pathogenesis of local inflammation-mediated bone loss.
authors.affiliation: University of Gothenburg, Gothenburg, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Engdahl
authors.forename: Catharina
authors.initials: C
authors.lastname: Lindholm
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stubelius
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Hans
authors.initials: H
authors.lastname: Carlsten
authors.forename: Marie K
authors.initials: MK
authors.lastname: Lagerquist
mesh_terms: D000818:Animals; D000941:Antigens / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D015519:Bone Density / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D020370:Osteoarthritis, Knee / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010024:Osteoporosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D013585:Synovitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*
chemical_list: D000941:Antigens; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D012710:Serum Albumin, Bovine; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
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