ADORA2A and periodontitis: To test whether adenosinergic signaling via A2aR would dampen periodontal inflammation, protecting the alveolar bone and conferring mitoprotective effects in gingival fibroblasts, we employed both an in vivo ligature-induced periodontitis model, administering CGS21680 throughout the disease course, and in vitro assays using Tnf-α-stimulated murine gingival fibroblasts pretreated with the agonist to dissect receptor-specific mechanisms underlying inflammation and bone loss prevention.