Inhibitory effects of dabigatran etexilate, a direct thrombin inhibitor, on osteoclasts and osteoblasts

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dc.creatorAmanda Leal Rocha
dc.creatorAdalberto Luiz Rosa
dc.creatorSandra Yasuyo Fukada
dc.creatorGisele Assis Castro Goulart
dc.creatorDaniel Dias Ribeiro
dc.creatorLucas Guimarães Abreu
dc.creatorTarcília Aparecida da Silva
dc.creatorRayana Longo Bighetti-Trevisan
dc.creatorLetícia Fernanda Duffles
dc.creatorJosé Alcides Almeida de Arruda
dc.creatorThaise Mayumi Taira
dc.creatorBruna Rodrigues Dias Assis
dc.creatorSoraia Macari
dc.creatorIvana Márcia Alves Diniz
dc.creatorMarcio Mateus Beloti
dc.date.accessioned2022-12-20T14:17:48Z
dc.date.accessioned2025-09-09T00:38:51Z
dc.date.available2022-12-20T14:17:48Z
dc.date.issued2020-02
dc.identifier.doihttps://doi.org/10.1016/j.thromres.2019.12.014
dc.identifier.issn00493848
dc.identifier.urihttps://hdl.handle.net/1843/48244
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofThrombosis Research
dc.rightsAcesso Restrito
dc.subjectAnticoagulants
dc.subjectDabigatran
dc.subjectThrombin
dc.subjectOsteoclasts
dc.subjectOsteoblasts
dc.subjectCells
dc.subjectCathepsin K
dc.subject.otherAnticoagulants
dc.titleInhibitory effects of dabigatran etexilate, a direct thrombin inhibitor, on osteoclasts and osteoblasts
dc.typeArtigo de periódico
local.citation.epage53
local.citation.spage45
local.citation.volume186
local.description.resumoIntroduction: Anticoagulants are widely used in orthopedic surgery to decrease the risk of deep vein thrombosis. While significant bone impairment is induced by long-term heparin therapy, little is known about the effects of direct oral anticoagulants (DOACs). Herein, we investigated the effects of dabigatran etexilate (Pradaxa®), a DOAC inhibitor of thrombin, on bone cells using in vitro and ex vivo cell culture models. Materials and methods: Osteoblasts and osteoclasts exposed to different concentrations of dabigatran etexilate and untreated cells were assayed for cell differentiation and activity. Favorable osteogenic conditions for osteoblasts were tested using titanium with nanotopography (Ti-Nano). In addition, mice treated with a dabigatran etexilate solution had bone marrow cells analyzed for the ability to generate osteoclasts. Results: Dabigatran etexilate at concentrations of 1 μg/mL and 2 μg/mL did not impact osteoclast or osteoblast viability. The drug inhibited osteoclast differentiation and activity as observed by the reduction of TRAP+ cells, resorption pits and gene and protein expression of cathepsin K. Consistently, osteoclasts from mice treated with dabigatran showed decreased area, resorptive activity, as well as gene and protein expression of cathepsin K. In osteoblast cultures, grown both on polystyrene and Ti-Nano, dabigatran etexilate reduced alkaline phosphatase (ALP) activity, matrix mineralization, gene expression of ALP and osteocalcin. Conclusions: Dabigatran etexilate inhibited osteoclast differentiation in ex vivo and in vitro models in a dose-dependent manner. Moreover, the drug reduced osteoblast activity even under optimal osteogenic conditions. This study provides new evidence regarding the negative overall impact of DOACs on bone cells.
local.publisher.countryBrasil
local.publisher.departmentFAO - DEPARTAMENTO DE ODONTOLOGIA RESTAURADORA
local.publisher.departmentFAO - DEPARTAMENTO DE ODONTOPEDIATRIA E ORTODONTIA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S004938481930547X?via%3Dihub

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