ROS Dependent Wnt/β-Catenin Pathway and Its Regulation on Defined Micro-Pillars—A Combined In Vitro and In Silico Study
Open accessAbstract
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.
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Some authors just calibrated their simulation models ([33, 46, 48, 49, 53, 57]).
“Some authors just calibrated their simulation models ([33, 46, 48, 49, 53, 57])”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [57]
Section 3.6 (In Silico; page unavailable) says fitting was used to obtain model dynamics for ICAT and SOX17, and Section 2.11 calls it a fitted model. But the paper also says the authors developed, extended, and used the model for simulation experiments, so “just calibrated” understates the work reported. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSix out of 19 publications recorded their own wet-lab data [28, 31, 32, 45, 51, 57].
“When looking at Wet-lab Data, six out of 19 publications recorded their own wet-lab data [28, 31, 32, 45, 51, 57].”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [57]
A second cluster forms around the simulation studies [45, 46, 51, 56, 57] and either includes the same wet-lab data from [105, 106], the Cell cycle [46] or ROS [51, 57].
“A second cluster forms around the simulation studies [45, 46, 51, 56, 57] and either includes the same wet-lab data from [105, 106], the Cell cycle [46] or ROS [51, 57].”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [57]
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- Authors
- Staehlke, S., Haack, F., Waldner, A.-C., Koczan, D., Moerke, C., Mueller, P., Uhrmacher, A. M., & Nebe, J. B.
- Affiliations
- Universitätsmedizin Rostock (DE)
- University of Rostock (DE)
- Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany
- Corresponding author
- Staehlke, Susanne
- ORCID
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2020-07-27
- Volume
- 9
- Issue
- 8
- Pages
- 1784
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC7464713
- OpenAlex
- W3044779240
- Cited by
- 36
- References
- 86
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 9 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 1
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 1270/1 - 299150580)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- Wnt/β-catenin signaling, reactive oxygen species, oxidative stress, micropillars, microtopography, MG-63 osteoblasts, β-catenin nuclear translocation, ICAT, transcriptional regulation, bone regeneration, mechanotransduction
- MeSH terms
- Computer Simulation, Humans, Reactive Oxygen Species, beta Catenin, Wnt Signaling Pathway, In Vitro Techniques
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