Desirable effect of combination therapy with high molecular weight hyaluronate and NSAIDs on MMP production

摘要: Summary Objective We previously reported that nonsteroidal anti-inflammatory drugs (NSAIDs) aggravated cartilage degeneration and hyaluronate (HA) reversed the destruction accelerated by NSAIDs in a rabbit osteoarthritis (OA) model. In present study, we analyzed mechanisms of these effects HA. Method An experimental model OA was induced partial meniscectomy treated with NSAIDs, HA combination over 2 weeks. After sacrifice, levels matrix metalloproteases (MMP)-1, MMP-3 MMP-13 synovial lavage fluid were measured. an vitro human articular chondrocytes cultured presence interleukin (IL)-1β or IL-6+sIL-6 for 24h. culture, production MMPs, IL-1β, IL-6 Results The MMP-1, from NSAID-treated group significantly higher than controls. increased MMPs counteracted concomitant administration studies showed augmented IL-1β- IL-6-induced chondrocytes, while completely inhibiting IL-6/sIL-6R-induced prostaglandin E (PGE ). addition PGE did not reduce augmentation MMP production. inhibited promotion cytokine-induced cytokine NSAIDs. Conclusions Our data clearly NSAID-accelerated which followed inflammatory cytokine-activated chondrocytes. results warrant further evaluation potential chondroprotective co-administration