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.
Highlights
Biofunctional materials which replace damaged tissue and stimulate cell regeneration are currently in great demand and will be in the future
The stabilization, accumulation, and translocation of the β-catenin into the nucleus is a marker for the activation of the Wnt/β-catenin pathway [15,16,23] and was examined by flow cytometry, laser scanning microscopy (LSM) and Western Blot within 24 h MG-63 cell cultivation on defined sharp-edged micro-pillars (P5)
In flow cytometry a significantly increase in total protein expression of β-catenin in cells on P5 compared with Ref after 24 h was observed (Figure 1A)
Summary
Biofunctional materials which replace damaged tissue and stimulate cell regeneration are currently in great demand and will be in the future. Titanium (Ti) and titanium-based alloys are the most common metallic materials in implant applications due to their good biocompatibility, mechanical compliance, and high corrosion resistance [1,2,3]. The rapid cellular acceptance in the tissue can be optimized by physico-chemical surface functionalization, e.g., topographical cues [4,5,6]. Cells are able to perceive the material surface properties and the extra cellular matrix. Initial cell adhesion [8] and downstream intracellular signaling cascades [9] determine the cell physiology and cell fate [10,11].
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