Metabolic responses of meniscal explants to injury and inflammation ex vivo.

This study was designed to characterize metabolic responses of meniscal tissue explants to injury and inflammation. We hypothesized that impact injury and interleukin (IL-1β) stimulation of meniscal explants would result in significant increases in matrix metalloproteinase (MMP) activity and relevant cytokine production compared to controls. Mature canine meniscal explants (n = 9/group) were randomly assigned to: (i) IL-1β (0.1 ng/ml) treated (IL); (ii) 25% strain (25); (iii) 75% strain (75); (iv) 25% + IL-1β (25IL); (v) 75% + IL-1β (75IL); or (vi) 0% + no IL-1β control (NC). Explants were impacted at 100 mm/s to 0%, 25%, or 75% strain and then cultured for 12 days with or without 0.1 ng/ml rcIL-1β. Media were refreshed every 3 days and analyzed for MMP activity, ADAMTS-4 activity, MMP-1, MMP-2, MMP-3, GAG, NO, PGE2 , IL-6, IL-8, MCP-1, and KC concentrations. Treatment with IL-1β alone significantly increased NO, PGE2, general MMP activity, IL-6, IL-8, KC, and MCP-1 media concentrations compared to negative controls. Impact at 75% significantly increased PGE2, IL-6, IL-8, and KC media concentrations compared to negative controls. The combination of IL-1β and 75% strain significantly increased production of PGE2 compared to IL-1β or 75% strain alone. Impact injury to meniscal explants ex vivo is associated with increased production of pro-inflammatory mediators and degradative enzyme activity, which are exacerbated by stimulation with IL-1β.