Norepinephrine modulates IL-1β-induced catabolic response of human chondrocytes

Background: The influence of the sympathetic nervous system (SNS) on metabolism of bone and cartilage expressing beta-adrenergic receptors (AR) was suggested. Here, we investigated whether the SNS functions as a modulator of cartilage metabolism induced by interleukin-1beta (IL-beta). Methods: Human articular chondrocytes and articular cartilage were collected from patients with osteoarthritis (OA). Chondrocyte monolayer and cartilage explant culture were stimulated with IL-1 beta. The activity of beta-ARs was modulated by an agonist, norepinephrine (NE), and antagonists, including propranolol, atenolol, nebivolol, and nadolol. Results: The levels of beta(1)-, beta(2)-, and beta(3)-AR in OA cartilage and IL-1 beta-treated chondrocytes were lower than normal cartilage and untreated cells. Treatment of chondrocytes with IL-1 beta and beta-blockers, including propranolol, atenolol, nebivolol, and nadolol, for 6 h significantly upregulated IL-1 beta-induced expression of MMP-1, -3, and - 13, compared to chondrocytes treated with IL-1 beta alone, indicating that antagonism of beta-AR confers catabolic signals. On the other hand, NE antagonized IL-1 beta-induced catabolic response. In addition, NE significantly inhibited IL-1 beta-induced release of glycosaminoglycan (GAG) from cartilage explant culture. In addition, beta-AR activity significantly affected IL-1 beta-stimulated phosphorylation of JNK and ERK. These results indicate that beta-AR signal is associated with cartilage metabolism. Conclusions: Our findings showed that B-ARs is a regulator of cartilage catabolism induced with IL-1 beta.