Abstract
In the last decade, skeletal muscle has been recognized as an endocrine organ able to release molecules that may act as paracrine or endocrine factors, namely myokines. Among these, irisin is secreted upon muscle contraction after physical exercise (PE) and has been demonstrated to yield anabolic effects on different cell types. Recently, irisin has been shown to improve cortical bone mass, geometry and strength, hence resembling the effect of PE. It has also been reported that irisin levels in the serum and synovial fluid of patients with knee osteoarthritis (OA) were negatively correlated with OA severity. Therefore, we hypothesized that irisin may improve cartilage metabolism and blunt the osteoarthritic process.
Human osteoarthritic chondrocytes (hOAC) were isolated from osteochondral specimens of patients undergoing total knee joint replacement. After in vitro expansion, hOAC were put in a three-dimensional culture system (alginate beads) and treated with either phosphate-buffered saline (control) or irisin (25 ng/mL). After 1 week, the amount of glycosaminoglycans (GAG) was evaluated using dimethylmethylene blue (DMMB) and PicoGreen assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect interleukin (IL)-1 and -6, matrix metalloproteinase (MMP)-1 and -13, inducible nitric oxide synthase (iNOS) and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and -3 gene expression levels.
hOAC treated with irisin showed a significant higher GAG content compared to the control group (p < 0.01). Moreover, irisin was able to reduce the expression of catabolic (MMP-1, -13, iNOS) and pro-inflammatory (IL-1, IL-6) markers, while incrementing the expression of TIMP-1 and -3 (p < 0.001).
Our results showed that irisin was able to stimulate GAG synthesis and diminish extracellular matrix catabolism in hOAC, demonstrating the existence of a cross-talk between cartilage and muscle possibly supporting the beneficial role of PE on cartilage homeostasis.
