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The Infl uence of Resveratrol on the Synovial Expression of Matrix Metalloproteinases and Receptor Activator of NF-țB Ligand in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

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The Infl uence of Resveratrol on the Synovial Expression of Matrix Metalloproteinases and Receptor Activator of NF-țB Ligand in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Mathias Glehra,*, Margherita Breisacha, Sonja Walzerb, Birgit Lohbergera, Florentine Fürstc, Joerg Friesenbichlera, Beate Rinnerd, Alexander Aviane, Reinhard Windhagerb, and Andreas Leithnera

a Department of Orthopaedic Surgery, Medical University of Graz,

Auenbruggerplatz 5, A-8036 Graz, Austria. E-mail: mathias.glehr@medunigraz.at

b Department of Orthopaedic Surgery, Medical University of Vienna, Währinger Gürtel 18 – 20, A-1090 Wien, Austria

c Department of Rheumatology, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria

d Center of Medical Research, Medical University of Graz, Stiftingtalstraße 24, A-8036 Graz, Austria

e Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Auenbruggerplatz 2, A-8036 Graz, Austria

* Author for correspondence and reprint requests

Z. Naturforsch. 68 c, 336 – 342 (2013); received July 30, 2012/May 21, 2013

Medication of rheumatoid arthritis (RA) remains challenging and often controversial con- cerning side effects or long-term complications. We investigated the effect of resveratrol, a phytoalexin discussed for its chondro-protective and anti-infl ammatory qualities, on the synovial expression of matrix-degrading enzymes like matrix metalloproteinases (MMPs) and bone-remodelling proteins in RA fi broblast-like synoviocytes (FLS). Interleukin-1ȕ- stimulated RA-FLS were treated with 100 µM resveratrol for 24 h. To evaluate the effect of resveratrol on the amount of bound/combined MMPs, a Luminex® xMAP multiplexing technology was used. The alteration in expression of receptor activator of nuclear factor- țB ligand (RANKL) and osteoprotegrin (OPG) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Resveratrol reduced the expression of MMP-1 (p = 0.022), MMP-3 (p = 0.021), and MMP-9 (p = 0.047). qRT-PCR showed a signifi cant reduction in the relative abundance of the transcripts of OPG (p = 0.012) and RANKL (p = 0.018).

Our in vitro fi ndings indicate that resveratrol could be a new target for further pharmaco- logical studies in the fi eld of RA. In the future it could play a role as a possible substitute or supplement to currently used drugs against RA to prevent cartilage matrix degradation and pathological bone resorption due to inhibition of MMPs and RANKL.

Key words: Resveratrol, Rheumatoid Arthritis, Matrix Metalloproteinases

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The Infl uence of Resveratrol on the Synovial Expression of Matrix Metalloproteinases and Receptor Activator of NF-κB Ligand in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

The alteration in expression of receptor activator of nuclear factor- κ B ligand (RANKL) and osteoprotegrin (OPG) was measured by quantitative real-time polymerase chain