Expression and regulation of human beta-defensin-2 in osteoarthritic cartilage

J Pathol. 2006 Jun;209(2):166-73. doi: 10.1002/path.1974.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Infective Agents / analysis*
  • Cartilage, Articular / chemistry*
  • Cells, Cultured
  • Chondrocytes / immunology
  • Chondrocytes / metabolism
  • Chondrocytes / microbiology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Humans
  • Immunohistochemistry / methods
  • Interleukin-1 / immunology
  • Interleukin-6 / immunology
  • Middle Aged
  • Osteoarthritis / genetics
  • Osteoarthritis / immunology
  • Osteoarthritis / metabolism*
  • Pseudomonas aeruginosa
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Tumor Necrosis Factor-alpha / immunology
  • Up-Regulation / genetics
  • beta-Defensins / analysis*
  • beta-Defensins / genetics

Substances

  • Anti-Infective Agents
  • DEFB4A protein, human
  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • beta-Defensins