title: Production of endogenous antibiotics in articular cartilage.
abstract: OBJECTIVE
  Defensins are broad-spectrum antimicrobial peptides that are components of innate immunity. To date, only epithelial surfaces and blood cells have been shown to produce these cationic peptides in bactericidal concentrations when challenged with microorganisms or inflammatory cytokines. Infections caused by gram-negative pathogens occur only infrequently in association with joint surgery. The present study was undertaken to investigate whether this may be explained by intraarticular production of gram-negative-specialized antimicrobial peptides.
  
  
  METHODS
  Healthy articular cartilage and cultured T/C-28a2 chondrocytes were assessed, by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, for expression of various antimicrobial peptides. The expression of human beta-defensin 2 (HBD-2) was studied in cultured chondrocytes after exposure to bacterial supernatants and proinflammatory cytokines and was assayed by real-time RT-PCR and immunoblot analysis. A septic arthritis mouse model was used to investigate the regulation of the murine homolog of HBD-2 in articular cartilage after bacterial inoculation.
  
  
  RESULTS
  Healthy articular cartilage and T/C-28a2 chondrocytes were able to produce different antimicrobial peptides. After exposure to gram-negative bacteria and proinflammatory cytokines, expression of cartilage-derived HBD-2 strongly increased. Immunoblot analysis revealed up-regulation of the gram-negative-specialized HBD-2 in microbicidal doses. Immunohistochemistry analysis revealed induction of the murine homolog of HBD-2 in vivo after intraarticular injection of bacteria.
  
  
  CONCLUSIONS
  This study demonstrated a previously unrecognized function of human chondrocytes. In addition to its biomechanical properties, articular cartilage has the ability to produce antimicrobial substances when challenged with microorganisms. The expression of HBD-2 in microbicidal doses suggests that antimicrobial peptides may contribute to host defense mechanisms in articular joints.
authors.affiliation: Schleswig-Holstein University and University Hospital, 24098 Kiel, Germany.
authors.forename: Deike
authors.initials: D
authors.lastname: Varoga
authors.forename: Thomas
authors.initials: T
authors.lastname: Pufe
authors.forename: Jürgen
authors.initials: J
authors.lastname: Harder
authors.forename: Ulf
authors.initials: U
authors.lastname: Meyer-Hoffert
authors.forename: Rolf
authors.initials: R
authors.lastname: Mentlein
authors.forename: Jens-Michael
authors.initials: JM
authors.lastname: Schröder
authors.forename: Wolf J
authors.initials: WJ
authors.lastname: Petersen
authors.forename: Bernhard N
authors.initials: BN
authors.lastname: Tillmann
authors.forename: Ehrhardt
authors.initials: E
authors.lastname: Proksch
authors.forename: Mary B
authors.initials: MB
authors.lastname: Goldring
authors.forename: Friedrich P
authors.initials: FP
authors.lastname: Paulsen
mesh_terms: D000328:Adult; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D001170:Arthritis, Infectious / Q000382:microbiology; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009994:Osmolar Concentration; D011552:Pseudomonas Infections / Q000378:metabolism; D013203:Staphylococcal Infections / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D023083:beta-Defensins / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins