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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.
AuthorsD Varoga, F P Paulsen, S Kohrs, S Grohmann, S Lippross, R Mentlein, B N Tillmann, M B Goldring, L Besch, T Pufe
JournalThe Journal of pathology (J Pathol) Vol. 209 Issue 2 Pg. 166-73 (Jun 2006) ISSN: 0022-3417 [Print] England
PMID16622898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright (c) 2006 Pathological Society of Great Britain and Ireland.
Chemical References
  • Anti-Infective Agents
  • DEFB4A protein, human
  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • beta-Defensins
Topics
  • Adult
  • Aged
  • Anti-Infective Agents (analysis)
  • Cartilage, Articular (chemistry)
  • Cells, Cultured
  • Chondrocytes (immunology, metabolism, microbiology)
  • Enzyme-Linked Immunosorbent Assay (methods)
  • Humans
  • Immunohistochemistry (methods)
  • Interleukin-1 (immunology)
  • Interleukin-6 (immunology)
  • Middle Aged
  • Osteoarthritis (genetics, immunology, metabolism)
  • Pseudomonas aeruginosa
  • RNA, Messenger (analysis)
  • Reverse Transcriptase Polymerase Chain Reaction (methods)
  • Tumor Necrosis Factor-alpha (immunology)
  • Up-Regulation (genetics)
  • beta-Defensins (analysis, genetics)

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