Reduction in matrix metalloproteinase production by tendon and synovial fibroblasts after a single exposure to 5-fluorouracil

This study investigated the effect of treatment with 5min exposures to 5-fluorouracil (5-FU) on the production of matrix metalloproteinases (MMPs) by endotenon and synovial fibroblasts. Fibroblasts were grown from the flexor tendons of New Zealand White rabbits and were then exposed to varying concentration<$>s (ranging from 0.25 mg ml−to 25 mg ml−of 5-FU for 5 min. The treated fibroblasts were suspended in a three-dimensional collagen lattice. The conditioned media from these collagen lattices were then analysed for MMP production using gelatin zymography on days 1, 3 and 7 after treatment. In the majority of cases this treatment produced a dose- and time-dependent reduction in total MMP production by both cell lines, specifically in the production of MMPs 2 and 9. This reduction was significant for most concentrations (P≤0.01–P≤0.05) when compared to phosphate-buffered-saline-treated controls. We conclude that 5-FU may reduce adhesions by limiting the migratory capacity of synovial fibroblasts (extrinsic healing).