IADR Abstract Archives
Protective Effects of Adenosine via A2aR in Experimental Periodontitis – Preliminary Results
Objectives: The study of the immune-inflammatory response affecting host metabolism can provide vital clues to early detection and prevention of tissue damage linked to periodontal inflammation. During inflammation, adenosine triphosphate (ATP) is released by dying cells as a ‘danger signal’, which activates and recruits immune cells. Extracellular ATP can ultimately be hydrolyzed into adenosine (ADO) which has a significant immunosuppressive effect and functions primarily to counteract pro-inflammatory ATP favoring tissue healing over excessive inflammation. We have recently demonstrated the important role of ADO in controlling gingival fibroblast inflammation-associated state in vitro, implicating mitochondrial function as a key mechanism in the pathogenesis of gingival hyper-inflammatory response. Adenosine initiates its biological effects by binding to adenosine receptors, including A2aR. Here, we explored the role of A2aR/adenosine signaling in experimental periodontitis.
Methods: We used the ligature-induced periodontitis (LIP) model placing the 5-0 silk ligature around the upper right second molar and left the upper left molar unligated to serve as an internal control for alveolar bone loss. During the 8 days of LIP, we treated one group of C57Bl/6J mice with an A2aR agonist (CGS21680, 0.1 mg/Kg). After 8 days of LIP, we assessed the alveolar bone loss by micro-CT and inflammatory cytokines in gingival tissue.
Results: We confirmed significant bone loss in the ligated site versus the unligated control site after 8 days of periodontitis induction. Our results indicate that animals treated with the A2aR agonist CGS21680 exhibited reduced bone loss compared to those treated with only vehicle, underscoring the anti-inflammatory role of adenosine signaling in oral tissues. Furthermore, we assessed the protein levels of inflammatory cytokines in local gingiva harvested from A2aR-treated mice with periodontitis. IL-1β was significantly decreased in A2aR-treated animals when compared with control (vehicle)-treated animals.
Conclusions: In conclusion, our preliminary data reveal the protective effects of adenosine signaling via A2aR in periodontitis.
Methods: We used the ligature-induced periodontitis (LIP) model placing the 5-0 silk ligature around the upper right second molar and left the upper left molar unligated to serve as an internal control for alveolar bone loss. During the 8 days of LIP, we treated one group of C57Bl/6J mice with an A2aR agonist (CGS21680, 0.1 mg/Kg). After 8 days of LIP, we assessed the alveolar bone loss by micro-CT and inflammatory cytokines in gingival tissue.
Results: We confirmed significant bone loss in the ligated site versus the unligated control site after 8 days of periodontitis induction. Our results indicate that animals treated with the A2aR agonist CGS21680 exhibited reduced bone loss compared to those treated with only vehicle, underscoring the anti-inflammatory role of adenosine signaling in oral tissues. Furthermore, we assessed the protein levels of inflammatory cytokines in local gingiva harvested from A2aR-treated mice with periodontitis. IL-1β was significantly decreased in A2aR-treated animals when compared with control (vehicle)-treated animals.
Conclusions: In conclusion, our preliminary data reveal the protective effects of adenosine signaling via A2aR in periodontitis.