ROS Dependent Wnt/β-Catenin Pathway and Its Regulation on Defined Micro-Pillars—A Combined In Vitro and In Silico Study

Staehlke, Susanne and Haack, Fiete and Waldner, Anna-Christin and Koczan, Dirk and Moerke, Caroline and Mueller, Petra and Uhrmacher, Adelinde M. and Nebe, J. Barbara (2020) ROS Dependent Wnt/β-Catenin Pathway and Its Regulation on Defined Micro-Pillars—A Combined In Vitro and In Silico Study. Cells, 9 (8), p. 1784. ISSN 2073-4409.

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Official URL: http://doi.org/10.3390/cells9081784

Abstract

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/β-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/β-catenin pathway. The β-catenin protein accumulated in the cytosol and translocated into the nucleus. Gene profiling indicated an antagonism mechanism of the transcriptional activity of β-catenin due to an increased expression of inhibitors like ICAT (inhibitor of β-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/β-catenin pathway, MG-63s are able to cope with an increased accumulation of β-catenin on micro-pillars and suppress an unintended target gene expression. Further, β-catenin may be diverted into other signaling pathways to support defense mechanisms against ROS.

Item Type: Article
Projects: LaCE