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

Autor(es)

Rocha, Fernanda R. G. ^{[1, 2]} ; Delitto, Andrea E. ^[3] ; Chaves de Souza, Joao A. ^[4] ; Gonzalez-Maldonado, Laura A. ^[2] ; Wallet, Shannon M. ^[5] ; Rossa Junior, Carlos ^[2]

Afiliação do(s) autor(es)

^[1] Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL 32610 - USA

^[2] UNESP State Univ Sao Paulo, Sch Dent Araraquara, Dept Diag & Surg, Araraquara, SP - Brazil

^[3] Univ Florida, Hlth Sci Ctr, Dept Phys Therapy, Gainesville, FL - USA

^[4] Fed Univ Goias UFG, Sch Dent, Dept Stomatol, Goiania, Go - Brazil

^[5] Univ N Carolina, Sch Dent, Dept Oral & Craniofacial Hlth Sci, Chapel Hill, NC 27515 - USA

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 MAY 8 2020.
• Citações Web of Science: 0

Resumo

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 mu CT 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-alpha 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. (AU)

• Processo FAPESP: 14/17544-6 - O inflamassomo NLRC4 e a resposta imune e perda óssea na doença periodontal experimental
• Beneficiário: Fernanda Regina Godoy Rocha
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 14/04926-8 - Inflamassomos NLRC4 e NLRP3 na doença periodontal experimental induzida por Aggregatibacter actinomycetemcomitans
• Beneficiário: Fernanda Regina Godoy Rocha
• Modalidade de apoio: Bolsas no Brasil - Doutorado