Clodronate disodium is neither cytotoxic nor cytoprotective to normal and recombinant equine interleukin-1β-treated joint tissues in vitro.

Abstract

To determine the effects of clodronate disodium (CLO) on control and recombinant equine interleukin-1β (IL-1β)-treated equine joint tissues. In vitro experimental study. Cartilage explants, chondrocytes, and synoviocytes (n=3 horses). Monolayer cultures of chondrocytes and synoviocytes from three horses were subjected to: control media (CON), 5ng/ml CLO (C/low), 50 ng/ml CLO (C/med), 100 ng/ml CLO (C/high), with and without IL-1β, and 10ng/ml IL-1β (IL) alone for 72 hours. Cartilage explants from three horses were subjected to CON, IL, C/low, and C/med with and without IL-1β for 72 hours. Culture media was analyzed for prostaglandin-E2 (PGE2 ), interleukin-6 (IL-6), and nitric oxide (NO). Explant media was analyzed for glycosaminoglycan (GAG) content and NO. At 72 hours, explant and monolayer culture viability were assessed, and explant GAG content was measured. IL-1β treatment resulted in higher media concentrations of GAG, NO, PGE2 , and IL-6 compared to the CON treatment (p < .05), demonstrating a catabolic effect of IL-1β on explants and monolayer cultures. CLO treatments did not increase media concentrations of GAG, NO, PGE2 , or IL-6 compared to CON, indicating no cytotoxic effect. Nevertheless, CLO treatments administered to IL-1β-treated monolayer cultures and explants did not significantly reduce the inflammatory response regardless of concentration. CLO did not demonstrate cytotoxic nor cytoprotective effects in normal and IL-1β-stimulated chondrocytes, synoviocytes or explants in culture. This study does not support the use of CLO as an anti-inflammatory treatment. Further research is necessary to confirm any anti-inflammatory effects of CLO on joint tissues.