Here we present evidence that activation of A2AR by intra-articular injection of liposomal adenosine and the potent and specific A2AR agonist CGS21680lows OA progression in two different models of established OA, a murine model of obesity-induced OA and a rat model of PTOA. This evidence concerns the gene ADORA2A and obesity due to melanocortin 4 receptor deficiency.