The effect of drugs commonly used in the treatment of equine articular disorders on the activity of equine matrix metalloproteinase-2 and 9.
Loss of articular cartilage, which is the most important pathological lesion occurring in osteoarthritis, has been shown to be enzymatically mediated. The matrix metalloproteinases (MMPs) are a group of enzymes which have been implicated in this degradation of articular cartilage matrix. The use of pharmacological agents to inhibit this catabolic process in the joint is a potential route for therapeutic intervention. The gelatinase MMPs, MMPs-2 and 9, were purified by affinity chromatography from equine cell cultures. The ability of phenylbutazone, flunixin, betamethasone, dexamethasone, methylprednisolone acetate (MPA), hyaluronan, pentosan polysulphate and polysulphated glycosaminoglycan (PSGAG) to inhibit equine MMPs-2 and 9 were assessed by two degradation assays. Whilst some agents did have direct effects on MMP activity, these effects were only obtained at concentrations which were unlikely to be achieved for any length of time in vivo. It is improbable that any pharmacological agent, currently used in the horse, has a significant effect on gelatinase MMP activity.
Clegg
P D
PD
Department of Veterinary Clinical Science and Animal Husbandry, University Veterinary Teaching Hospital, University of Liverpool, Leahurst, Neston, UK.
Jones
M D
MD
Carter
S D
SD
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D017364:Collagenases / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism*; D006734:Horse Diseases / Q000188:drug therapy / Q000201:enzymology*; D006736:Horses / Q000502:physiology*; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D010003:Osteoarthritis / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary*
D018501:Antirheumatic Agents; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9