Varoga D, Paulsen F P, Kohrs S, Grohmann S, Lippross S, Mentlein R, Tillmann B N, Goldring M B, Besch L, Pufe T
Department of Orthopaedic and Trauma Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
J Pathol. 2006 Jun;209(2):166-73. doi: 10.1002/path.1974.
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.
防御素是一类抗生素肽，参与上皮和间充质表面的宿主防御。先前的研究表明，骨关节炎关节中可诱导人β-防御素-3（HBD-3）的产生，这表明这些分子除了具有杀灭微生物的能力外，还具有其他功能。本研究的目的是调查另一种人β-防御素HBD-2在骨关节炎（OA）中的产生情况，并确定其受炎性细胞因子的调控方式。通过逆转录聚合酶链反应（RT-PCR）、免疫组织化学和酶联免疫吸附测定（ELISA）评估健康和骨关节炎软骨中的HBD-2表达。培养C28/I2软骨细胞、原代软骨细胞和软骨外植体用于体外研究。在用肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）或IL-6刺激24小时后，进行实时RT-PCR和ELISA实验，以评估这些细胞因子对HBD-2产生的影响。与健康软骨不同，在所检查的大多数OA样本（十分之八）中都发现了HBD-2的表达。通过实时RT-PCR和ELISA测定，OA发病机制中可能涉及的细胞因子TNF-α、IL-1和IL-6是体外培养的软骨细胞和软骨外植体中HBD-2的转录诱导剂。这些结果说明了HBD-2在骨关节炎软骨中的诱导作用，并表明它是OA发病机制中的另一个因素。然而，需要进一步研究以阐明HBD-2在骨关节炎软骨中所起的作用。
