Therapeutic potential of N-acetyl cysteine (NAC) in a human ex vivo cartilage trauma-model
The mechanical trauma of articular cartilage can cause cell loss and cytokine-driven inflammatory response. Subsequent accumulation of reactive oxygen (ROS) and nitrogen (RNS) species boosts the enzymatic degradation of extracellular matrix (ECM). A study was done to deduce the therapeutic potential of N-acetyl cysteine (NAC) in a human ex vivo cartilage trauma-model, shedding light on cell and chondroprotective features.
Human full-thickness cartilage explants were subjected to a defined impact trauma (0.59 J) and managed with NAC. The efficiency of NAC administration was estimated by: cell viability, apoptosis rate, anabolic/catabolic gene expression, secretion and activity of matrix metalloproteinases (MMPs) and proteoglycan (PG) release.
The results disclosed that continuous NAC administration increased cell viability and lower the apoptosis rate after trauma. It also concealed trauma-induced gene expression of ECM-destructive enzymes, like ADAMTS-4, MMP-1, -2, -3 and -13 in a dosage- and time-depending manner. On protein level, subsequent suppression of MMP-2 and MMP-13 secretion reflected these findings on protein level. Additionally, NAC inhibited proteolytic activity of MMPs and reduced PG release. This study depicted not only remarkable cell and chondroprotective features, but also showed novel encouraging findings related to therapeutically effective concentration and treatment-time regimen of NAC. NAC was recommended as a multifunctional add-on reagent for pharmaceutical intervention after cartilage injury as due to it’s defense against chondrocyte apoptosis and catabolic enzyme secretion.
All in all, this data aided in increasing our knowledge on the therapeutic potential of NAC after cartilage trauma and presents a foundation for future in vivo studies.