Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, 98125 Messina, Italy.
Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, 98125 Messina, Italy.
Biochem Biophys Res Commun. 2018 May 15;499(3):506-512. doi: 10.1016/j.bbrc.2018.03.178. Epub 2018 Mar 31.
Serglycin is expressed by a variety of cell types and mediates different functions in both normal and pathological conditions by interacting with different biological molecules, such as the CD44 receptor. Many studies suggest that serglycin has a crucial role in inflammatory response, but there are limited data on the functions of this proteoglycan in chondrocytes. In this study we investigated the effect of serglycin knockdown induced by a specific serglycin small interfering RNA (SRGN siRNA) in normal mouse chondrocytes stimulated with lipopolysaccharide (LPS). LPS administration in normal chondrocytes increased the expression of serglycin mRNA and related protein and the production of the pro-inflammatory mediators TNF-alpha, IL-1beta, IL-6, iNOS and MMP-9, through NF-kB activation. In addition, a marked increased expression of CD44 after LPS stimulation was observed. Notably, the CD44 expression and the inflammatory response were significantly reduced by SRGN siRNA treatment in LPS treated chondrocytes. Similar results were obtained in normal mouse chondrocytes exposed to LPS, using a specific blocking antibody against CD44. These results indicate that serglycin produced in LPS-induced inflammation in normal mouse chondrocytes is able to modulate inflammation by interacting with CD44 receptor, suggesting a possible key role in the cartilage inflammation.
硫酸软骨素蛋白聚糖在多种细胞类型中表达，并通过与不同的生物分子（如 CD44 受体）相互作用，在正常和病理条件下发挥不同的功能。许多研究表明，硫酸软骨素蛋白聚糖在炎症反应中具有关键作用，但关于该蛋白聚糖在软骨细胞中的功能的资料有限。在这项研究中，我们研究了特异性硫酸软骨素蛋白聚糖小干扰 RNA (SRGN siRNA) 诱导的正常小鼠软骨细胞中硫酸软骨素蛋白聚糖敲低对脂多糖 (LPS) 刺激的影响。LPS 处理正常软骨细胞后，通过 NF-κB 激活，增加了硫酸软骨素蛋白聚糖 mRNA 和相关蛋白的表达，以及促炎介质 TNF-α、IL-1β、IL-6、iNOS 和 MMP-9 的产生。此外，在 LPS 刺激后观察到 CD44 的表达明显增加。值得注意的是，在 LPS 处理的软骨细胞中，用 SRGN siRNA 处理可显著降低 CD44 的表达和炎症反应。在 LPS 暴露的正常小鼠软骨细胞中使用针对 CD44 的特异性阻断抗体也获得了类似的结果。这些结果表明，在 LPS 诱导的正常小鼠软骨细胞炎症中产生的硫酸软骨素蛋白聚糖能够通过与 CD44 受体相互作用来调节炎症，提示其在软骨炎症中可能具有关键作用。
