Relevance of Caspase-1 and Nlrp3 Inflammasome on Inflammatory Bone Resorption in A Murine Model of Periodontitis

<jats:title>Abstract</jats:title><jats:p>This study investigates the role of NLRP3 inflammasome and its main effector Caspase-1 in inflammation and alveolar bone resorption associated with periodontitis. Heat-killed <jats:italic>Aggregatibacter actinomycetemcomitans</jats:italic> (Aa) was injected 3x/week (4 weeks) into gingival tissues of wild-type (WT), <jats:italic>Nlrp3</jats:italic>-KO and <jats:italic>Caspase1</jats:italic>-KO mice. Bone resorption was measured by µCT and osteoclast number was determined by tartrate-resistant acid phosphatase (TRAP) staining. Inflammation was assessed histologically (H/E staining and immunofluorescence of CD45 and Ly6G). <jats:italic>In vitro</jats:italic> studies determined the influence of Nlrp3 and Caspase-1 in Rankl-induced osteoclast differentiation and activity and on LPS-induced expression of inflammation-associated genes. Bone resorption was significantly reduced in <jats:italic>Casp1</jats:italic>-KO but not in <jats:italic>Nlrp3</jats:italic>-KO mice. <jats:italic>Casp1</jats:italic>-KO mice had increased in osteoclast numbers, whereas the inflammatory infiltrate or on gene expression were similar to those of WT and <jats:italic>Nlrp3</jats:italic>-KO mice. Strikingly, osteoclasts differentiated from <jats:italic>Nlrp3</jats:italic>-deficient macrophages had increased resorbing activity <jats:italic>in vitro</jats:italic>. LPS-induced expression of Il-10, Il-12 and Tnf-α was significantly reduced in <jats:italic>Nlrp3</jats:italic>- and <jats:italic>Casp1</jats:italic>-deficient macrophages. As an inceptive study, these results suggest that Nlrp3 inflammasome does not play a significant role in inflammation and bone resorption <jats:italic>in vivo</jats:italic> and that Caspase-1 has a pro-resorptive role in experimental periodontal disease.</jats:p>