Advanced glycation end products (AGEs) are a group of stable covalent compounds generated by proteins, lipids, other macromolecules and sugar through a series of non-enzymatic reactions. As reported, AGEs can cause widespread pathophysiological responses through activation of AGE receptors (RAGEs) on the cell surface, and play an important role in the pathogenesis of osteoarthritis (OA). We hypothesized that the antioxidant and anti-glycan agent gallic acid (GA) can work against the effects of AGEs and can be used as a potential drug for the cure of OA.
The present study first explored the negative functions of AGEs via AGE-treated chondrocytes isolated form rabbits. Then, we observed the protective role of GA in AGE-treated chondrocytes by measuring the reactive oxygen species (ROS), superoxide dismutase (SOD), collagen II, aggrecan, nitric oxide synthase (iNOs) and cyclooxygenase-2 (COX-2) in vitro. Finally, the changes in a cartilage lesion in a rabbit model of knee osteoarthritis was observed.
Exposure of chondrocytes to AGEs resulted in a reduction of ROS, SOD, collagen II and aggrecan, and an increase in iNOs and COX-2, which means exposure promoted OA lesions in a clinical setting. When AGE-treated chondrocytes were pretreated with GA, there were no significant changes in these key components compared to the normal chondrocytes. In vivo study showed cartilage degradation was reduced by GA as compared to the vehicle group.
The results of this study confirmed the chondroprotective role of GA and provide a potential drug for the relief of OA.