Department of Biomedical and Dental Sciences and Morphofunctional Images, Policlinico Universitario, University of Messina, 98125 Messina, Italy.
Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, 98125 Messina, Italy.
Arch Biochem Biophys. 2018 Feb 15;640:75-82. doi: 10.1016/j.abb.2018.01.007. Epub 2018 Jan 13.
Cartilage degeneration are hallmarks of wear, tear, mechanical and inflammatory damage of the joint cartilage. Tissue degradation as well as compromising the integrity and function of the organ, produces different intermediates, directly able to stimulate further inflammatory effect, therefore, amplifying the inflammation response. Biglycan is a soluble component of the extracellular matrix that is released during tissue injury. It has been reported that released biglycan is an endogenous ligand for TLR-2/4 in some cell type. We studied the role of biglycan in an experimental model of biglycan-induced inflammatory response in human chondrocytes and the effect of high polymerized HA on reducing its activity. Exposition of chondrocytes to LPS generated cell injury, including high levels of biglycan. Chondrocyte treatment with biglycan produces a high mRNA expression of several detrimental inflammation mediators such as IL-1β, IL-6, MMP-13, and IL-17, as well as NF-kB and TLR-4 activation. Administration of high polymerized HA to chondrocytes exposed to biglycan was able to attenuate the inflammatory response by decreasing the expression of the inflammatory mediators. Involvement of the TLR-4 in the mediation of the biglycan action was confirmed using a specific silent agent (siRNA). Taken together, these data could be used to develop new anti-inflammatory approaches.
软骨退变是关节软骨磨损、撕裂、机械和炎症损伤的标志。组织降解以及损害器官的完整性和功能，会产生不同的中间产物，这些中间产物直接能够刺激进一步的炎症效应，从而放大炎症反应。核心蛋白聚糖是细胞外基质的一种可溶性成分，在组织损伤时会被释放。据报道，在某些细胞类型中，释放的核心蛋白聚糖是 TLR-2/4 的内源性配体。我们研究了核心蛋白聚糖在人软骨细胞中核心蛋白聚糖诱导的炎症反应实验模型中的作用，以及高分子量 HA 降低其活性的作用。LPS 暴露会导致软骨细胞损伤，包括高水平的核心蛋白聚糖。核心蛋白聚糖处理软骨细胞会产生几种有害炎症介质的高 mRNA 表达，如 IL-1β、IL-6、MMP-13 和 IL-17，以及 NF-kB 和 TLR-4 的激活。将高分子量 HA 施用于暴露于核心蛋白聚糖的软骨细胞能够通过降低炎症介质的表达来减弱炎症反应。使用特定的沉默剂（siRNA）证实了 TLR-4 参与了核心蛋白聚糖作用的介导。综上所述，这些数据可用于开发新的抗炎方法。
