IADR Abstract Archives
The Role of CD73 in Periodontitis
Objectives: Periodontitis is an immune-mediated inflammatory disease affecting almost half of the adult population and is the leading cause of tooth loss in the United States. The role of extracellular nucleotide signaling including nucleotide metabolizing enzyme CD73 adds an important layer of interaction of purine mediators capable of orchestrating inflammatory outcomes. CD73 is an ectonucleotidase able to catabolize 5′-adenosine monophosphate (AMP) into adenosine at the extracellular level. Extracellular adenosine plays a critical role in regulating many processes under physiological and pathological conditions. Our group has previously shown CD73-dependent adenosine dampens chemokine CXCL8 secretion in gingival stromal cells suggesting adenosine-related anti-inflammatory effects may provide vital clues for controlling inflammatory bone loss. Here, we explored the role of CD73 in ligature-induced periodontitis in vivo comparing wild-type C57Bl6 and CD73-deficient mice.
Methods: We assessed gingival levels of inflammatory cytokines in vivo through RT-qPCR, bone loss through micro-CT and RANKL-induced osteoclastogenesis in vitro. We have also performed analysis of CD73 mRNA in samples derived from patients diagnosed with severe periodontitis.
Results: Our results show the lack of CD73 resulted in increased inflammatory cytokines such as Interleukin (IL)-1β, IL-17, CXCL1 and CXCL2 in diseased gingiva relative to the healthy-contralateral side and in comparison with the wild type controls. CD73-deficient animals also showed increased osteoclastogenesis in vitro. Micro-CT analysis revealed the lack of CD73 resulted in decreased bone mineral density, decreased trabecular bone volume and thickness as well as decreased bone volume in vivo. We have also confirmed the relevance of our results in human periodontitis as samples derived from severe (Grade C) periodontitis showed decreased levels of CD73 compared to healthy controls.
Conclusions: In conclusion, CD73 has an essential protective role in the gingival periodontal tissue and bone homeostasis, being an important candidate for future target therapies to control immune-mediated inflammatory disorders.
Methods: We assessed gingival levels of inflammatory cytokines in vivo through RT-qPCR, bone loss through micro-CT and RANKL-induced osteoclastogenesis in vitro. We have also performed analysis of CD73 mRNA in samples derived from patients diagnosed with severe periodontitis.
Results: Our results show the lack of CD73 resulted in increased inflammatory cytokines such as Interleukin (IL)-1β, IL-17, CXCL1 and CXCL2 in diseased gingiva relative to the healthy-contralateral side and in comparison with the wild type controls. CD73-deficient animals also showed increased osteoclastogenesis in vitro. Micro-CT analysis revealed the lack of CD73 resulted in decreased bone mineral density, decreased trabecular bone volume and thickness as well as decreased bone volume in vivo. We have also confirmed the relevance of our results in human periodontitis as samples derived from severe (Grade C) periodontitis showed decreased levels of CD73 compared to healthy controls.
Conclusions: In conclusion, CD73 has an essential protective role in the gingival periodontal tissue and bone homeostasis, being an important candidate for future target therapies to control immune-mediated inflammatory disorders.