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Cells ; 9(8)2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32726949

RESUMO

The physico-chemical surface design of implants influences the surrounding cells. Osteoblasts on sharp-edged micro-topographies revealed an impaired cell phenotype, function and Ca2+ mobilization. The influence of edges and ridges on the Wnt/ß-catenin pathway in combination with the cells' stress response has not been clear. Therefore, MG-63 osteoblasts were studied on defined titanium-coated micro-pillars (5 × 5 × 5 µm) in vitro and in silico. MG-63s on micro-pillars indicated an activated state of the Wnt/ß-catenin pathway. The ß-catenin protein accumulated in the cytosol and translocated into the nucleus. Gene profiling indicated an antagonism mechanism of the transcriptional activity of ß-catenin due to an increased expression of inhibitors like ICAT (inhibitor of ß-catenin and transcription factor-4). Cells on pillars produced a significant reactive oxygen species (ROS) amount after 1 and 24 h. In silico analyses provided a detailed view on how transcriptional activity of Wnt signaling is coordinated in response to the oxidative stress induced by the micro-topography. Based on a coordinated expression of regulatory elements of the Wnt/ß-catenin pathway, MG-63s are able to cope with an increased accumulation of ß-catenin on micro-pillars and suppress an unintended target gene expression. Further, ß-catenin may be diverted into other signaling pathways to support defense mechanisms against ROS.


Assuntos
Espécies Reativas de Oxigênio/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/metabolismo , Simulação por Computador , Humanos , Técnicas In Vitro
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