Pivotal role of NOD2 in inflammatory processes affecting atherosclerosis and periodontal bone loss

Apolipoprotein E^−/− (ApoE^−/−) mice deficient in nucleotide binding oligomerization domain-containing protein 2 (NOD2) and subjected to an oral gavage of Porphyromonas gingivalis developed elevated serum inflammatory cytokines, cholesterol, alveolar bone loss, and atherosclerosis. Stimulation of NOD2 by Muramyl DiPeptide (MDP) in ApoE^−/− mice reduced P. gingivalis-induced inflammatory cytokines, cholesterol, alveolar bone loss, and atherosclerosis by reducing the expression of inhibitor of NF-κB kinase-β, NF-κB, JNK mRNA, and TNF-α protein levels. A reduction in body weight gain was observed in ApoE^−/− mice fed a high-fat diet (HFD) and injected with MDP compared to ApoE^−/− mice fed a HFD but saline injected. MDP activation of NOD2 should be considered in the treatment of inflammatory processes affecting atherosclerosis, bone loss, and possibly, weight gain.