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 –Induced Stimulation of Caspase-3 and Cleavage of PARP in Human Articular Chondrocytes in Vitro
a Musculoskeletal Research Group, Institute of Anatomy, Ludwig-Maximilian-University Munich, 80336 Munich, Germany b Charité Medicine University Berlin, Campus Benjamin Franklin, Department for Trauma Surgery, 14195 Berlin, Germany c Division of Veterinary Medicine, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Leicestershire, LE12 5RD, UK
Key Words: osteoarthritis • chondrocyte • IL-1  • apoptosis • caspase-3 • PARP • resveratrol
Address for correspondence: Dr. Mehdi Shakibaei, Institute of Anatomy, Musculoskeletal Research Group, Ludwig-Maximilian-University Munich, Pettenkoferstrasse 11, D-80336 Munich. Voice: +49-89-5160-4827; fax: +49-89-5160-4828. e-mail: mehdi.shakibaei{at}med.uni-muenchen.de
Resveratrol is a polyphenolic phytoalexin that is present in various fruits, in the skin of red grapes and peanuts. Recent studies have shown that resveratrol exhibits potent antioxidant properties and is able to exert anti-inflammatory and anti-catabolic properties in several cell types. The pro-inflammatory cytokine interleukin-1
(IL-1) plays a pivotal role in the pathogenesis of osteoarthritis (OA) in humans and animals. In this article we investigated whether resveratrol is able to block the effects of IL-1, specifically the activation of caspase-3 and subsequent cleavage of poly (ADP-ribose) polymerase (PARP) in human articular chondrocytes. Cultures of human chondrocytes were prestimulated with 10 ng/mL IL-1 for 1, 12, and 24 h before being co-treated with IL-1 and 100 µM resveratrol or 50 µM of the caspase inhibitor Z-DEVD-FMK for 1, 12, and 24 h, respectively in vitro. Resveratrol significantly reduced the IL-1-induced inhibition of expression of cartilage-specific collagen type II and signal transduction receptor 1-integrin in a time-dependent manner. Incubation of chondrocytes with IL-1 resulted in the activation of caspase-3 and PARP cleavage. These effects were abolished through co-treatment with resveratrol. Furthermore, co-treatment of IL-1-stimulated cells with the caspase inhibitor Z-DEVD-FMK blocked activation of caspase-3 and PARP cleavage, suggesting that this process is a caspase-dependent pathway. In summary, our results confirm that resveratrol is an effective inhibitor of chondrocyte apoptosis in vitro. These findings suggest that this dietary polyphenolic compound may have future applications in the nutraceutical-based therapy of human and animal OA.
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