These authors contributed equally to this work.
Cytoprotective and anti-inflammatory effects of melatonin in hydrogen peroxide-stimulated CHON-001 human chondrocyte cell line and rabbit model of osteoarthritis via the SIRT1 pathway
Article first published online: 17 APR 2012
© 2012 John Wiley & Sons A/S
Journal of Pineal Research
Volume 53, Issue 3, pages 225–237, October 2012
How to Cite
Lim, H.-D., Kim, Y.-S., Ko, S.-H., Yoon, I.-J., Cho, S.-G., Chun, Y.-H., Choi, B.-J. and Kim, E.-C. (2012), Cytoprotective and anti-inflammatory effects of melatonin in hydrogen peroxide-stimulated CHON-001 human chondrocyte cell line and rabbit model of osteoarthritis via the SIRT1 pathway. Journal of Pineal Research, 53: 225–237. doi: 10.1111/j.1600-079X.2012.00991.x
- Issue published online: 10 SEP 2012
- Article first published online: 17 APR 2012
- Accepted manuscript online: 19 MAR 2012 05:12AM EST
- Received November 14, 2011; Accepted March 12, 2012.
- anti-inflammatory effects;
- hydrogen peroxide;
Abstract: Melatonin has potent antioxidant, analgesic, and antinociceptive properties. However, the effects of melatonin against oxidative stress-induced cytotoxicity and inflammatory mediators in human chondrocytes remain poorly understood. This study examined the effects and underlying mechanism of melatonin in hydrogen peroxide (H2O2)-stimulated human chondrocytes and rabbit osteoarthritis (OA) model. Melatonin markedly inhibited hydrogen peroxide (H2O2)-stimulated cytotoxicity, iNOS, and COX-2 protein and mRNA expression, as well as the downstream products, NO and PGE2. Incubation of cells with melatonin decreased H2O2-induced Sirtuin 1 (SIRT1) mRNA and protein expression. SIRT1 inhibition by sirtinol or Sirt1 siRNA reversed the effects of melatonin on H2O2-mediated induction of pro-inflammatory cytokines (NO, PGE2, TNF-α, IL-1β, and IL-8) and the expression of iNOS, COX-2, and cartilage destruction molecules. Melatonin blocked H2O2-induced phosphorylation of PI3K/Akt, p38, ERK, JNK, and MAPK, as well as activation of NF-κB, which was reversed by sirtinol and SIRT1 siRNA. In rabbit with OA, intra-articular injection of melatonin significantly reduced cartilage degradation, which was reversed by sirtinol. Taken together, this study shows that melatonin exerts cytoprotective and anti-inflammatory effects in an oxidative stress-stimulated chondrocyte model and rabbit OA model, and that the SIRT1 pathway is strongly involved in this effect.