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.

摘要: Melatonin has potent antioxidant, analgesic, and antinociceptive properties. However, the effects of melatonin against oxidative stress-induced cytotoxicity inflammatory mediators in human chondrocytes remain poorly understood. This study examined underlying mechanism hydrogen peroxide (H(2) O(2) )-stimulated rabbit osteoarthritis (OA) model. markedly inhibited cytotoxicity, iNOS, COX-2 protein mRNA expression, as well downstream products, NO PGE(2) . Incubation cells with decreased H(2) -induced Sirtuin 1 (SIRT1) expression. SIRT1 inhibition by sirtinol or Sirt1 siRNA reversed on -mediated induction pro-inflammatory cytokines (NO, , TNF-α, IL-1β, IL-8) expression COX-2, cartilage destruction molecules. blocked phosphorylation PI3K/Akt, p38, ERK, JNK, MAPK, activation NF-κB, which was siRNA. In OA, intra-articular injection significantly reduced degradation, sirtinol. Taken together, this shows that exerts cytoprotective anti-inflammatory an stress-stimulated chondrocyte model OA model, pathway is strongly involved effect.