Antioxidative therapy in an ex vivo human cartilage trauma-model: Attenuation of trauma-induced cell loss and ECM-destructive enzymes by N-acetyl cysteine

• Published in: Osteoarthritis and cartilage 2016-12, Vol.24 (12), p.2171-2180
• Main Authors: Riegger, J, Joos, H, Palm, H.G, Friemert, B, Reichel, H, Ignatius, A, Brenner, R.E
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Cartilage; Cell protection; Chondrocytes; Chondroprotection; ECM degradation; Extracellular Matrix; Humans; Mechanical loading; N-acetyl cysteine; Posttraumatic osteoarthritis; Proteoglycans; Rheumatology
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2016.07.019

Summary Objective Mechanical trauma of articular cartilage results in cell loss and cytokine-driven inflammatory response. Subsequent accumulation of radical oxygen (ROS) and nitrogen (RNS) species enhances the enzymatic degradation of the extracellular matrix (ECM). This study aims on the therapeutic potential of N-acetyl cysteine (NAC) in a human ex vivo cartilage trauma-model, focusing on cell- and chondroprotective features. Design Human full-thickness cartilage explants were subjected to a defined impact trauma (0.59 J) and treated with NAC. Efficiency of NAC administration was evaluated by following outcome parameter: cell viability, apoptosis rate, anabolic/catabolic gene expression, secretion and activity of matrix metalloproteinases (MMPs) and proteoglycan (PG) release. Results Continuous NAC administration increased cell viability and reduced the apoptosis rate after trauma. It also suppressed trauma-induced gene expression of ECM-destructive enzymes, such as ADAMTS-4, MMP-1, -2, -3 and -13 in a dosage- and time-depending manner. Subsequent suppression of MMP-2 and MMP-13 secretion reflected these findings on protein level. Moreover, NAC inhibited proteolytic activity of MMPs and reduced PG release. Conclusion In the context of this ex vivo study, we showed not only remarkable cell- and chondroprotective features, but also revealed new encouraging findings concerning the therapeutically effective concentration and treatment-time regimen of NAC. Its defense against chondrocyte apoptosis and catabolic enzyme secretion recommends NAC as a multifunctional add-on reagent for pharmaceutical intervention after cartilage injury. Taken together, our data increase the knowledge on the therapeutic potential of NAC after cartilage trauma and presents a basis for future in vivo studies.