Leukotriene B4 Loaded in Microspheres Inhibits Osteoclast Differentiation and Activation

• Autor(a) principal: Lorencetti-Silva,Francine
• Data de Publicação: 2022
• Outros Autores: Arnez,Maya Fernanda Manfrin, Thomé,João Pedro de Queiroz, Carvalho,Marcio Santos de, Carvalho,Fabrício Kitazono de, Queiroz,Alexandra Mussolino de, Faccioli,Lúcia Helena, Paula-Silva,Francisco Wanderley Garcia
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Brazilian Dental Journal
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-64402022000500035
• topic: Osteoclast; leukotriene B4; macrophages; differentiation; activation; microsphere

Abstract To investigate osteoclast formation in vivo and if leukotriene B4 (LTB4) loaded in microspheres (MS) could be used as a therapeutical strategy to promote a sustained delivery of the mediator and prevent osteoclast differentiation. Methods: In vivo, apical periodontitis was induced in mice to investigate osteoclast differentiation and signaling in absence of 5-lipoxygenase (5-LO). In vitro, LTB4-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process. Characterization and efficiency of LTB4 encapsulation were investigated. J774A.1 macrophages were cultured in the presence of monocyte colony-stimulating factor (M-CSF) and ligand for receptor activator of nuclear factor kappa B (RANKL) and then stimulated with LTB4-MS. Cytotoxicity, in vitro MS-LTB4 uptake, osteoclast formation and gene expression were measured. Results: We found that 5-LO negatively regulates osteoclastic formation in vivo during apical periodontitis development. In vitro, LTB4-MS were up-taken by macrophages and were not cytotoxic to the cells. LTB4-MS inhibited osteoclast formation and the synthesis of osteoclastogenic genes Acp5, Mmp9, Calcr and Ctsk. LTB4-MS inhibited differentiation of macrophages into an osteoclastic phenotype and cell activation under M-CSF and RANKL stimulus.