Author(s): Rocha, Fernanda R G. [UNESP] ; Delitto, Andrea E. ; de Souza, Joao A. Chaves ; González-Maldonado, Laura A. [UNESP] ; Wallet, Shannon M. ; Rossa Junior, Carlos [UNESP]
Date: 2020
Persistent ID: http://hdl.handle.net/11449/200378
Origin: Oasisbr
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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 Aggregatibacter actinomycetemcomitans (Aa) was injected 3x/week (4 weeks) into gingival tissues of wild-type (WT), Nlrp3-KO and Caspase1-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). In vitro 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 Casp1-KO but not in Nlrp3-KO mice. Casp1-KO mice had increased in osteoclast numbers, whereas the inflammatory infiltrate or on gene expression were similar to those of WT and Nlrp3-KO mice. Strikingly, osteoclasts differentiated from Nlrp3-deficient macrophages had increased resorbing activity in vitro. LPS-induced expression of Il-10, Il-12 and Tnf-α was significantly reduced in Nlrp3- and Casp1-deficient macrophages. As an inceptive study, these results suggest that Nlrp3 inflammasome does not play a significant role in inflammation and bone resorption in vivo and that Caspase-1 has a pro-resorptive role in experimental periodontal disease.
Department of Oral Biology College of Dentistry University of Florida
Department of Diagnosis and Surgery UNESP-State University of Sao Paulo School of Dentistry at Araraquara
Department of Physical Therapy University of Florida Health Science Center
Department of Stomatology School of Dentistry Federal University of Goias (UFG)
Department of Oral and Craniofacial Health Sciences School of Dentistry University of North Carolina
Department of Diagnosis and Surgery UNESP-State University of Sao Paulo School of Dentistry at Araraquara
FAPESP: 2014/04926-8
FAPESP: 2014/17544-6
CAPES: AUXPE 655/2014
