title: Changes in MMP-2 and -9 activity and MMP-8 reactivity after amphotericin B induced synovitis and treatment with bufexamac.
abstract: The objective here was to evaluate the acute effects of induced arthritis on synovial fluid (SF) levels of matrix metalloproteinases (MMP) -2, -8 and -9 in horses. To evaluate MMP-2 and -9 activities and the effect of non-steroidal anti-inflammatory drug (NSAID) bufexamac during remission from acute arthritis. Aseptic arthritis was induced in 24 Standardbred horses using 20 mg of amphotericin B as a single intra-articular (IA) injection in the right intercarpal joint. After 1 week and 2 weeks, horses were treated intra-articularly with 10, 20, or 40 mg of bufexamac suspension or with sterile saline solution as control. SF was sampled prior to induction and at weekly intervals for 5 weeks. Fluids were evaluated for MMP-2 and MMP-9 activity by gelatin zymography or for MMP-8 immunoreactivity by Western Blotting. IA injection of amphotericin B consistently resulted in significant increase in the immunoreactivity of MMP-8 and activity of both the latent and the active forms of MMP-2 and -9, among which the active form of MMP-2 increased the most. MMP-9 levels declined to pre-induction levels within 2 weeks, whereas levels of MMP-2 remained still high after 5 weeks. Treatment with bufexamac did not significantly affect levels of gelatinolytic MMP. Results suggest that after acute arthritis of horses, elevated MMP activity is present in the joint, for several weeks, to a degree that could promote cartilage degradation, and treatment with the NSAID bufexamac is not likely to affect that. Furthermore, analysing levels of MMP-9 activity and especially levels of active forms of MMP-2 activity may be valuable to predict the time of occurrence of arthritis in horses.
authors.affiliation: Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, 00014 HU, Finland. piia.marttinen@helsinki.fi
authors.forename: P H
authors.initials: PH
authors.lastname: Marttinen
authors.forename: S M
authors.initials: SM
authors.lastname: Raulo
authors.forename: M M
authors.initials: MM
authors.lastname: Suominen
authors.forename: R-M
authors.initials: RM
authors.lastname: Tulamo
mesh_terms: D000666:Amphotericin B / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002019:Bufexamac / Q000627:therapeutic use*; D005260:Female; D006734:Horse Diseases / Q000188:drug therapy / Q000201:enzymology*; D006736:Horses; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011897:Random Allocation; D013582:Synovial Fluid / Q000737:chemistry; D013585:Synovitis / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D002019:Bufexamac; D000666:Amphotericin B; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9