Abstract
Irisin is a hormone-like myokine released from skeletal muscle during exercise. It has also been reported that irisin levels in serum and synovial fluid of knee osteoarthritis (OA) patients were negatively correlated with OA severity. We hypothesized that irisin might play a role in the cartilage homeostasis mediated by physical activity. Therefore, this study aims to explore the cross talk between skeletal muscle and cartilage tissues in human with OA mediated by the myokine irisin. Human articular OA chondrocytes were isolated, expanded and cultured in micro-mass 3-D culture system. Pellets were cultured with or without r-Irisin, and then activated by protein inhibitors of p38-MAPK signalling pathway. After one week the amount of GAG content was evaluated. Quantitative gene expression of Coll-X and Coll-II was performed. WB was utilized to detect expressions of p38-MAPK signalling pathway and Coll-X and Coll-II. In the current study, chondrocytes cultured in r-Irisin showed a significant higher GAG/DNA content compared to control (p<0.05). Moreover, r-Irisin promoted a significant increase of the expression collagen type II and decrease of collagen type X in (p<0.05). This OA chondrocytes recovery was abrogated by the p38 MAPK and ERK signalling pathways. Our observation suggests that Irisin targets chondrocytes promoting GAG content, increasing Collagen Type II and decreasing Collagen type X gene expressions. The observed OA chondrocyte recovery mediated by irisin is obtained through the inactivation of p38/ERK MAP kinase signalling cascades in vitro. This is the first study that demonstrates a cross-talk between muscle and cartilage mediated by irisin.
