Expression and regulation of human beta-defensin-2 in osteoarthritic cartilage.
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.
Varoga
D
D
Department of Orthopaedic and Trauma Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Germany. deikevaroga@hotmail.com
Paulsen
F P
FP
Kohrs
S
S
Grohmann
S
S
Lippross
S
S
Mentlein
R
R
Tillmann
B N
BN
Goldring
M B
MB
Besch
L
L
Pufe
T
T
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
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