title: Expression and regulation of human beta-defensin-2 in osteoarthritic cartilage.
abstract: Defensins are antibiotic peptides that are involved in host defence at epithelial and mesenchymal surfaces. Previous studies have shown the induction of human beta-defensin-3 (HBD-3) in osteoarthritic joints, suggesting that these molecules have functions in addition to their ability to kill microbes. The aim of this study was to investigate the production of a further human beta-defensin, named HBD-2, in osteoarthritis (OA) and to determine its regulation by inflammatory cytokines. Healthy and osteoarthritic cartilage was assessed for HBD-2 expression by RT-PCR, immunohistochemistry, and ELISA. C28/I2 chondrocytes, primary chondrocytes, and cartilage explants were cultured for in vitro studies. After 24 h of stimulation with tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) or IL-6, real-time RT-PCR and ELISA experiments were performed to evaluate the effect of these cytokines on the production of HBD-2. In contrast to healthy cartilage, HBD-2 expression was identified in most of the OA samples examined (eight of ten). Cytokines that are potentially involved in the pathogenesis of OA, namely TNF-alpha, IL-1, and IL-6, were transcriptional inducers of HBD-2 in cultured chondrocytes and cartilage explants in vitro, as measured by real-time RT-PCR and ELISA. These results illustrate the induction of HBD-2 in osteoarthritic cartilage and suggest that it is a further factor in the pathogenesis of OA. However, further studies are required to elucidate the role played by HBD-2 in osteoarthritic cartilage.
authors.affiliation: Department of Orthopaedic and Trauma Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Germany. deikevaroga@hotmail.com
authors.forename: D
authors.initials: D
authors.lastname: Varoga
authors.forename: F P
authors.initials: FP
authors.lastname: Paulsen
authors.forename: S
authors.initials: S
authors.lastname: Kohrs
authors.forename: S
authors.initials: S
authors.lastname: Grohmann
authors.forename: S
authors.initials: S
authors.lastname: Lippross
authors.forename: R
authors.initials: R
authors.lastname: Mentlein
authors.forename: B N
authors.initials: BN
authors.lastname: Tillmann
authors.forename: M B
authors.initials: MB
authors.lastname: Goldring
authors.forename: L
authors.initials: L
authors.lastname: Besch
authors.forename: T
authors.initials: T
authors.lastname: Pufe
mesh_terms: D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000032:analysis*; D002358:Cartilage, Articular / Q000737:chemistry*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011550:Pseudomonas aeruginosa; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics; D023083:beta-Defensins / Q000032:analysis* / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; C106641:DEFB4A protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins