The Multifarious Functions of Leukotrienes in Bone Metabolism

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Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorSanford Burnham Prebys Medical Discovery Institute-
Autor(es): dc.contributorUniversity of Zürich-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversity Center of Adamantina-
Autor(es): dc.contributorFaculdades de Dracena-
Autor(es): dc.creatorAmadeu de Oliveira, Flávia-
Autor(es): dc.creatorTokuhara, Cintia K.-
Autor(es): dc.creatorVeeriah, Vimal-
Autor(es): dc.creatorDomezi, João Paulo-
Autor(es): dc.creatorSantesso, Mariana R.-
Autor(es): dc.creatorCestari, Tania M.-
Autor(es): dc.creatorVentura, Talita M.O.-
Autor(es): dc.creatorMatos, Adriana A.-
Autor(es): dc.creatorDionísio, Thiago-
Autor(es): dc.creatorFerreira, Marcel R.-
Autor(es): dc.creatorOrtiz, Rafael C.-
Autor(es): dc.creatorDuarte, Marco A.H.-
Autor(es): dc.creatorBuzalaf, Marília A.R.-
Autor(es): dc.creatorPonce, José B.-
Autor(es): dc.creatorSorgi, Carlos A.-
Autor(es): dc.creatorFaccioli, Lucia H.-
Autor(es): dc.creatorBuzalaf, Camila Peres-
Autor(es): dc.creatorde Oliveira, Rodrigo Cardoso-
Data de aceite: dc.date.accessioned2025-08-21T16:31:18Z-
Data de disponibilização: dc.date.available2025-08-21T16:31:18Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2023-08-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1002/jbmr.4867-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/307515-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/307515-
Descrição: dc.descriptionLeukotrienes (LTs) are derived from arachidonic acid metabolism by the 5-lipoxygenase (5-LO) enzyme. The production of LTs is stimulated in the pathogenesis of rheumatoid arthritis (RA), osteoarthritis, and periodontitis, with a relevant contribution to bone resorption. However, its role in bone turnover, particularly the suppression of bone formation by modulating the function of osteoclasts and osteoblasts, remains unclear. We investigated the effects of LTs on bone metabolism and their impact on osteogenic differentiation and osteoclastogenesis using a 5-LO knockout (KO) mouse model. Results from micro-computed tomography (μCT) analysis of femur from 8-week-old 5-LO-deficient mice showed increased cortical bone and medullary region in females and males and decreased trabecular bone in females. In the vertebra, we observed increased marrow area in both females and males 5-LO KO and decreased trabecular bone only in females 5-LO KO. Immunohistochemistry (IHC) analysis showed higher levels of osteogenic markers tissue-nonspecific alkaline phosphatase (TNAP) and osteopontin (OPN) and lower expression of osteoclastogenic marker tartrate-resistant acid phosphatase (TRAP) in the femurs of 5-LO KO mice versus wild-type (WT). Alkaline phosphatase activity and mineralization assay results showed that the 5-LO absence enhances osteoblasts differentiation and mineralization but decreases the proliferation. Alkaline phosphatase (ALP), Bglap, and Sp7 gene expression were higher in 5-LO KO osteoblasts compared to WT cells. Eicosanoids production was higher in 5-LO KO osteoblasts except for thromboxane 2, which was lower in 5-LO–deficient mice. Proteomic analysis identified the downregulation of proteins related to adenosine triphosphate (ATP) metabolism in 5-LO KO osteoblasts, and the upregulation of transcription factors such as the adaptor-related protein complex 1 (AP-1 complex) in long bones from 5-LO KO mice leading to an increased bone formation pattern in 5-LO–deficient mice. We observed enormous differences in the morphology and function of osteoclasts with reduced bone resorption markers and impaired osteoclasts in 5-LO KO compared to WT osteoclasts. Altogether, these results demonstrate that the absence of 5-LO is related to the greater osteogenic profile. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).-
Descrição: dc.descriptionEndocrine Fellows Foundation-
Descrição: dc.descriptionMarie Curie-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionBauru School of Dentistry University of São Paulo, SP-
Descrição: dc.descriptionHuman Genetics Program Sanford Children's Health Research Center Sanford Burnham Prebys Medical Discovery Institute-
Descrição: dc.descriptionInstitute for Regenerative Medicine University of Zürich-
Descrição: dc.descriptionRibeirão Preto Medical School University of São Paulo, SP-
Descrição: dc.descriptionInstitute of Biosciences São Paulo State University-UNESP, SP-
Descrição: dc.descriptionDepartment of Medicine University Center of Adamantina, SP-
Descrição: dc.descriptionDepartment of Medicine Faculdades de Dracena, SP-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences of Ribeirão Preto University of São Paulo, SP-
Descrição: dc.descriptionInstitute of Biosciences São Paulo State University-UNESP, SP-
Descrição: dc.descriptionCAPES: 88881.030354/2013-01-
Formato: dc.format1135-1153-
Idioma: dc.languageen-
Relação: dc.relationJournal of Bone and Mineral Research-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subject5-LIPOXYGENASE-
Palavras-chave: dc.subjectBONE LOSS-
Palavras-chave: dc.subjectINFLAMMATORY DISEASES-
Palavras-chave: dc.subjectLEUKOTRIENES-
Palavras-chave: dc.subjectOSTEOBLASTS-
Palavras-chave: dc.subjectOSTEOCLASTOGENESIS-
Título: dc.titleThe Multifarious Functions of Leukotrienes in Bone Metabolism-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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