4 '-hydroxy aceclofenac suppresses the interleukin-1-induced production ofpromatrix metalloproteinases and release of sulfated-glycosaminoglycans from rabbit articular chondrocytes

This study demonstrates the novel actions of a non-steroidal anti-inflammat ory drug aceclofenac, which is frequently used for rheumatoid arthritis and osteoarthritis. 4'-Hydroxy aceclofenac, a main metabolite of aceclofenac i n humans, down-regulated the production of promatrix metalloproteinase-1/pr ocollagenase 1 and promatrix metalloproteinase-3/prostromelysin 1 along wit h a decrease in their mRNAs in rabbit articular chondrocytes and synoviocyt es, and interfered with the release of sulfated-glycosaminoglycans (proteog lycans) from the chondrocytes. 4'-Hydroxy aceclofenac also suppressed thr p roliferation of rabbit synoviocytes. In contrast, aceclofenac itself and it s other metabolites, diclofenac and 4'-hydroxy declofenac, did not exert ob vious actions on cellular functions. Therefore, it is suggested that the th erapeutic effects of aceclofenac on rheumatoid arthritis and osteoarthrits are, at least in part, due to the novel chondroprotective effect of 4'-hydr oxy aceclofenac via the suppression of promatrix metalloproteinase producti on and proteoglycan release. There is also evidence that inhibition of syno viocyte proliferation and the known inhibitory action on prostaglandin E-2 production play a role, (C) 2000 Elsevier Science B.V. All rights reserved.