ADORA2A and arthritic joint disease: Indeed, methotrexate treatment diminishes wear particle-induced osteolysis via adenosine ligation of A2AR (Mediero et al., 2015) and A2AR agonists reduce bone resorption and disease progression in an animal model of type II collagen-induced arthritis (Bitto et al., 2011; Mazzon et al., 2011).