title: The relevance of leukotrienes for bone resorption induced by mechanical loading.
abstract: 5-Lipoxygenase (5-LO) metabolites are important pro-inflammatory lipid mediators. However, much still remains to be understood about the role of such mediators in bone remodeling. This study aimed to investigate the effect of 5-LO metabolites, LTB4 and CysLTs, in a model of mechanical loading-induced bone remodeling. Strain-induced tooth movement and consequently alveolar bone resorption/apposition was achieved by using a coil spring placed on molar and attached to incisors of C57BL6 (wild-type-WT), 5-LO deficient mice (5-LO(-/-)) and mice treated with 5-LO inhibitor (zileuton-ZN) or with antagonist of CysLTs receptor (montelukast-MT). The amount of bone resorption and the number of osteoclasts were determined morphometrically. The expression of inflammatory and bone remodeling markers in periodontium was analyzed by qPCR. Osteoclast differentiation and TNF-α production were evaluated in vitro using RAW 264.7 cells treated with LTB4 or LTD4. Bone resorption, TRAP(+) cells and expression of Tnfa, Il10 and Runx2 were significantly diminished in 5-LO(-/-), ZN- and MT-treated mice. The expression of Rank was also reduced in 5-LO(-/-) and MT-treated mice. Accordingly, LTB4 and LTD4 in association with RANKL promoted osteoclast differentiation and increased TNF-α release in vitro. These data demonstrate that the absence of 5-LO metabolites, LTB4 and CysLTs reduces osteoclast recruitment and differentiation, consequently diminishing bone resorption induced by mechanical loading. Thus, 5-LO might be a potential target for controlling bone resorption in physiological and pathological conditions.
authors.affiliation: Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil; Department of Oral Pathology and Surgery, Faculty of Dentistry, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: A P
authors.initials: AP
authors.lastname: Moura
authors.affiliation: Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: S R A
authors.initials: SR
authors.lastname: Taddei
authors.affiliation: Department of Oral Pathology and Surgery, Faculty of Dentistry, Universidade Federal de Minas Gerais, Minas Gerais, Brazil; Department of Microbiology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: C M
authors.initials: CM
authors.lastname: Queiroz-Junior
authors.affiliation: Department of Oral Pathology and Surgery, Faculty of Dentistry, Universidade Federal de Minas Gerais, Minas Gerais, Brazil; Department of Microbiology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: M F M
authors.initials: MF
authors.lastname: Madeira
authors.affiliation: Department of Oral Pathology and Surgery, Faculty of Dentistry, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: L F D
authors.initials: LF
authors.lastname: Rodrigues
authors.affiliation: Department of Biological Sciences, School of Dentistry of Bauru, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: G P
authors.initials: GP
authors.lastname: Garlet
authors.affiliation: Department of Microbiology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: D G
authors.initials: DG
authors.lastname: Souza
authors.affiliation: Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: F S
authors.initials: FS
authors.lastname: Machado
authors.affiliation: Department of Dentistry, Pontifícia Universidade Católica de Minas Gerais, Minas Gerais, Brazil.
authors.forename: I
authors.initials: I
authors.lastname: Andrade
authors.affiliation: Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: M M
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Department of Oral Pathology and Surgery, Faculty of Dentistry, Universidade Federal de Minas Gerais, Minas Gerais, Brazil. Electronic address: tarcilia@ufmg.br.
authors.forename: T A
authors.initials: TA
authors.lastname: Silva
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001862:Bone Resorption / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D007975:Leukotriene B4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical
chemical_list: D015289:Leukotrienes; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase
keywords: Bone remodeling; Leukotriene inhibitors; Orthodontic tooth movement