Temporal Effects of Cytokine Treatment on Lubricant Synthesis and MMP Activity of Fibroblast ‐like Synoviocytes

This study assessed the HA, lubricin, and matrix metalloproteinase‐2 (MMP‐2) secretion profile of FLS over 12 days of culture. FLS were subjected to continuous, intermittent, and s equential cytokine treatments of interleukin‐1 beta (IL‐1β), tumor necrosis factor‐alpha (TNF‐α), and transforming growth factor‐beta 1 (TGF‐β1). HA was assessed via an ELISA‐like assay for content, and agarose gel electrophoresis for molecular weight distribution. Relative lubricin content was determined by western blot. Pro MMP‐2 and active MMP‐2 were quantified by gelatin zymography. All intermittent and sequential treatments significantly increased secretion of high MW (>3 MDa) HA for the duration of the culture. Sequentially treated groups elevated lubricin synthesis, while only groups receiving IL ‐1β and TNF‐α for 2 days followed by TGF‐β1 for 1 day reduced active MMP‐2 to unstimulated control levels. These data provide important information on the long‐term functional potential of cytokine stimulated FLS, and suggests that temporal regulation of cytokine exposure can be a power ful tool to guide healthy synovial secretions.

Source: Journal of Tissue Engineering and Regenerative Medicine - November 7, 2018 Category: Biotechnology Authors: Ahmad Abu ‐Hakmeh, Allison K.M. Fleck, Leo Q. Wan Tags: RESEARCH ARTICLE Source Type: research