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Rheumatology Advance Access originally published online on March 27, 2008
Rheumatology 2008 47(5):627-633; doi:10.1093/rheumatology/ken116
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Diacerein has a weak effect on the catabolic pathway of human osteoarthritis synovial fibroblast—comparison to its effects on osteoarthritic chondrocytes

M. A. Álvarez-Soria, G. Herrero-Beaumont, O. Sánchez-Pernaute, M. Bellido and R. Largo

Joint and Bone Research Unit, Fundación Jiménez Díaz, Autonomous University, Madrid, Spain.

Correspondence to: R. Largo, Joint and Bone Research Unit, Rheumatology Department, Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040 Madrid, Spain. E-mail: rlargo{at}fjd.es


   Abstract

Objectives. Synoviocytes play a crucial role in the inflammatory response leading to structural damage in OA. Our aim was to assess the effects of diacerein and NSAIDs on cellular responses of synoviocytes associated with inflammation and structural integrity of cartilage in OA.

Methods. The effects of diacerein, celecoxib, diclofenac, meloxicam and indomethacin on prostaglandin (PG) E2 production, cyclo-oxygenase-2 (COX-2) protein expression, nitrite levels, presence of MMP-1 and -13, and activation of nuclear factor-{kappa}B (NF-{kappa}B) were studied on stimulated OA synoviocytes and chondrocytes.

Results. Diacerein and NSAIDs inhibited IL-1β-stimulated NF-{kappa}B activation in synoviocytes and chondrocytes except indomethacin in synoviocytes. Diacerein further increased COX-2 protein expression and PGE2 synthesis in synoviocytes stimulated with IL-1β, while no effect was observed on stimulated chondrocytes. NSAIDs diminished until almost basal levels PGE2 release in both cells and, surprisingly, these drugs also diminished COX-2 protein expression both in synoviocytes and chondrocytes. With regard to structural mediators, diacerein decreased MMP-13 levels in synoviocytes but did not modify MMP-1 presence. NSAIDs induced a significant increase in MMP-1 levels in both cell types and in MMP-13 levels in chondrocytes.

Conclusions. Diacerein does not seem to reduce but rather increase inflammatory mediators in synoviocytes, while it does not overall affect chondrocyte inflammatory profile.

KEY WORDS: Osteoarthritis, Cytokines and inflammatory mediators, Extracellular matrix, Synovium, Non-steroidal anti-inflammatory drugs

Submitted 2 November 2007; revised version accepted 15 February 2008.
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