The influence of resveratrol on the synovial expression of matrix metalloproteinases and receptor activator of NF-kappaB ligand in rheumatoid arthritis fibroblast-like synoviocytes.
Medication of rheumatoid arthritis (RA) remains challenging and often controversial concerning side effects or long-term complications. We investigated the effect of resveratrol, a phytoalexin discussed for its chondro-protective and anti-inflammatory qualities, on the synovial expression of matrix-degrading enzymes like matrix metalloproteinases (MMPs) and bone-remodelling proteins in RA fibroblast-like synoviocytes (FLS). Interleukin-1beta-stimulated RA-FLS were treated with 100 microM 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-kappaB 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 significant reduction in the relative abundance of the transcripts of OPG (p = 0.012) and RANKL (p = 0.018). Our in vitro findings indicate that resveratrol could be a new target for further pharmacological studies in the field 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.
Department of Orthopaedic Surgery, Medical University of Graz, Auenbruggerplatz 5, A-8036 Graz, Austria. mathias.glehr@medunigraz.at
Mathias
M
Glehr
Margherita
M
Breisach
Sonja
S
Walzer
Birgit
B
Lohberger
Florentine
F
Fürst
Joerg
J
Friesenbichler
Beate
B
Rinner
Alexander
A
Avian
Reinhard
R
Windhager
Andreas
A
Leithner
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D053245:RANK Ligand / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D053245:RANK Ligand; D013267:Stilbenes; C505688:TNFSF11 protein, human; D020782:Matrix Metalloproteinases; D000077185:Resveratrol