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 concentrations (ranging from 0.25 mg x ml(-1)to 25 mg x ml(-1)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< or =0.01-P< or =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).
Ragoowansi
R
R
Phoenix Tissue Repair Unit, Department of Plastic and Reconstructive Surgery, University College London, London, UK.
Khan
U
U
Brown
R A
RA
McGrouther
D A
DA
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000187:drug effects*; D011817:Rabbits; D013583:Synovial Membrane / Q000166:cytology; D013710:Tendons / Q000166:cytology; D013997:Time Factors
D000963:Antimetabolites; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D005472:Fluorouracil