Chondroprotective effects and mechanisms of resveratrol in advanced glycation end products-stimulated chondrocytes
1 Graduate Institute of Medical Science, National Defense Medical Center, Neihu 114, Taipei, Taiwan, ROC
2 Division of Rheumatology/Immunology & Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Neihu 114, Taipei, Taiwan, ROC
3 Institute of Cellular and System Medicine, National Health Research Institute, Zhunan, Miaoli County 350, Taiwan, ROC
4 Graduate Institute of Basic Medical Science, PhD Program of Aging, China Medical University, Taichung 40402, Taiwan, ROC
Arthritis Research & Therapy 2010, 12:R167 doi:10.1186/ar3127Published: 8 September 2010
Accumulation of advanced glycation end products (AGEs) in joints contributes to the pathogenesis of cartilage damage in osteoarthritis (OA). We aim to explore the potential chondroprotective effects of resveratrol on AGEs-stimulated porcine chondrocytes and cartilage explants.
Chondrocytes were isolated from pig joints. Activation of the IκB kinase (IKK)-IκBα-nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)-activator protein-1 (AP-1) pathways was assessed by electrophoretic mobility shift assay (EMSA), Western blot and transfection assay. The levels of inducible nitric oxide synthase (iNOS)-NO and cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) were measured by Western blot, Griess reaction or ELISA. The expression and enzyme activity of matrix metalloproteinase-13 (MMP-13) were determined by real time RT/PCR and gelatin zymography, respectively.
We show that AGEs-induced expression of iNOS and COX-2 and production of NO and PGE2 were suppressed by resveratrol. Such effects of resveratrol were likely mediated through inhibiting IKK-IκBα-NF-κB and JNK/ERK-AP-1 signaling pathways induced by AGEs. By targeting these critical signaling pathways, resveratrol decreased AGEs-stimulated expression and activity of MMP-13 and prevented AGEs-mediated destruction of collagen II. Histochemistry analysis further confirms that resveratrol could prevent AGEs-induced degradation of proteoglycan and aggrecan in cartilage explants.
The present study reveals not only the effects and mechanisms regarding how resveratrol may protect cartilage from AGEs-mediated damage but also the potential therapeutic benefit of resveratrol in the treatment of OA.