Effects of 5-lipoxygenase gene disruption on inflammation, osteoclastogenesis and bone resorption in polymicrobial apical periodontitis

Autor(es)

Garcia Paula-Silva, Francisco Wanderley ^{[1, 2]} ; Manfrin Arnez, Maya Fernanda ^[1] ; Ferreira Petean, Igor Bassi ^[1] ; Almeida-Junior, Luciano Aparecido ^[1] ; Bezerra da Silva, Raquel Assed ^[1] ; Bezerra da Silva, Lea Assed ^[1] ; Faccioli, Lucia Helena ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Pediat Dent, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Lab Inflamacao & Imunol Parasitoses, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ARCHIVES OF ORAL BIOLOGY; v. 112, APR 2020.
• Citações Web of Science: 0

Resumo

Objectives: To investigate the regulation of inflammatory and osteoclastogenic signaling by 5-lipoxygenase (5-LO) in apical periodontitis induced by oral contamination of dental root canals in mice. Design: Apical periodontitis was induced in 5-lipoxygenase enzyme knockout (129-Alox5(tm1fun)) and 129 wild-type mice (n = 96) by exposure of the dental root canal to the oral cavity. After 7, 14, 21, and 28 days, the animals were euthanized and the tissues removed (n = 12 teeth per period) for histopathological and histometric analyses (hematoxylin and eosin {[}HE]), evaluation of osteoclastogenic activity (tartrate-resistant acid phosphatase enzyme {[}TRAM), and determination of inflammatory and osteoclastogenic signaling (qRT-PCR). Results: Oral contamination of dental root canals induced recruitment of neutrophils and osteoclasts to the periodontal ligament, resulting in bone resorption. Absence of 5-LO did not impair neutrophil recruitment while osteoclastic formation was increased. Nonetheless, early bone resorption progressed similarly to lesions in wildtype animals. Interestingly, in the absence of 5-LO, the synthesis of mRNAs for cytokines, chemokines, and their receptors was significantly reduced while that of regulators of osteoclastogenesis (RANK, RANKL, and OPG) was increased in comparison with the corresponding levels in wild-type animals. Conclusions: The 5-LO pathway plays a role in the stimulation of inflammatory mediator synthesis and inhibition of osteoclastogenesis in apical periodontitis in mice. However, the paradoxical inflammatory-osteoclastogenic signaling did not impair inflammatory cell recruitment and bone resorption during early development of the disease. (AU)

• Processo FAPESP: 10/17611-4 - Mecanismos envolvidos na modulação da via 5-lipoxigenase na lesão periapical experimentalmente induzida
• Beneficiário: Francisco Wanderley Garcia de Paula e Silva
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 12/01292-2 - Papel da Enzima 5-Lipoxigenase na Osteoclastogênese durante o Desenvolvimento da Lesão Periapical Experimental
• Beneficiário: Igor Bassi Ferreira Petean
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica