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Type:	Artigo de Periódico
Title:	Inhibitory effects of dabigatran etexilate, a direct thrombin inhibitor, on osteoclasts and osteoblasts
Authors:	Amanda Leal Rocha Adalberto Luiz Rosa Sandra Yasuyo Fukada Gisele Assis Castro Goulart Daniel Dias Ribeiro Lucas Guimarães Abreu Tarcília Aparecida da Silva Rayana Longo Bighetti-Trevisan Letícia Fernanda Duffles José Alcides Almeida de Arruda Thaise Mayumi Taira Bruna Rodrigues Dias Assis Soraia Macari Ivana Márcia Alves Diniz Marcio Mateus Beloti
Abstract:	Introduction: 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.
Subject:	Anticoagulants Dabigatran Thrombin Osteoclasts Osteoblasts Cells Cathepsin K
language:	eng
metadata.dc.publisher.country:	Brasil
Publisher:	Universidade Federal de Minas Gerais
Publisher Initials:	UFMG
metadata.dc.publisher.department:	FAO - DEPARTAMENTO DE ODONTOLOGIA RESTAURADORA FAO - DEPARTAMENTO DE ODONTOPEDIATRIA E ORTODONTIA
Rights:	Acesso Restrito
metadata.dc.identifier.doi:	https://doi.org/10.1016/j.thromres.2019.12.014
URI:	http://hdl.handle.net/1843/48244
Issue Date:	Feb-2020
metadata.dc.url.externa:	https://www.sciencedirect.com/science/article/pii/S004938481930547X?via%3Dihub
metadata.dc.relation.ispartof:	Thrombosis Research
Appears in Collections:	Artigo de Periódico

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