Liraglutide suppresses TNF-α-induced degradation of extracellular matrix in human chondrocytes: a therapeutic implication in osteoarthritis.

Osteoarthritis (OA) is a major global health problem; however, the etiology of the disease remains unknown and a reliable treatment strategy has yet to be discovered. Modulation of the receptor for glucagon-like peptide 1 (GLP-1) has emerged as a potential treatment strategy for various diseases including OA. In the present study, we investigated the effects of the specific GLP-1 receptor agonist liraglutide on factors of the pathogenesis of OA induced by tumor necrosis factor-α (TNF-α), including oxidative stress, expression of proinflammatory cytokines, degradation of articular cartilage extracellular matrix, and activation of the nuclear factor-κB (NF-κB) pathway. Our findings demonstrate that liraglutide exerted a potent beneficial effect in human primary chondrocytes by downregulating generation of reactive oxygen species and NADPH oxidase 4, suppressing expression of interleukin-6 and monocyte chemoattractant protein 1, rescuing type II collagen and aggrecan from degradation my matrix metalloproteinases and a disintegrin and metalloproteinase with type I thrombospondin motif, and inhibiting activation of the proinflammatory NF-κB signaling pathway. These findings demonstrate a potential role of GLP-1 receptor in the pathogenesis of OA and lay a foundation for further research on the mechanisms behind the potential therapeutic application of liraglutide in the treatment and prevention of OA.