Lixisenatide attenuates advanced glycation end products (AGEs)-induced degradation of extracellular matrix in human primary chondrocytes

Abstract

Osteoarthritis (OA) poses a growing threat to the health of the global population. Accumulation of advanced glycation end-products (AGEs) has been shown to upregulate expression of degradative enzymes such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) in chondrocytes, which leads to excessive degradation of type II collagen and aggrecan in the articular extracellular matrix (ECM). In the present study we investigated the effects of the GLP-1 agonist lixisenatide, a widely used type II diabetes medication, on AGEs-induced decreased mitochondrial membrane potential (MMP), degradation of ECM, oxidative stress, expression of cytokines including interleukin (IL)-1β and IL-6, and activation of nuclear factor kappa B (NF-κB). Our findings indicate that lixisenatide significantly ameliorated the deleterious effects of AGEs in a dose-dependent manner. Thus, lixisenatide has potential as a safe and effective treatment for OA and other AGEs-induced inflammatory diseases.

Keywords

• Lixisenatide
• osteoarthritis
• type II collagen
• aggrecan
• metalloproteinases (MMPs)
• a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)