Canonical Wnt signaling enhances pro-inflammatory response to titanium by macrophages

Biomaterial characteristics like surface roughness and wettability can determine the phenotype of macrophages following implantation. We have demonstrated that inhibiting Wnt ligand secretion abolishes macrophage polarization in vitro and in vivo; however, the role of canonical Wnt signaling in macr...

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Bibliographic Details
Published in:Biomaterials 2022-10, Vol.289, p.121797-121797, Article 121797
Main Authors: Avery, Derek, Morandini, Lais, Sheakley, Luke S., Shah, Arth H., Bui, Loc, Abaricia, Jefferson O., Olivares-Navarrete, Rene
Format: Article
Language:English
Subjects:
Anti-Inflammatory Agents - metabolism
Biocompatible Materials - chemistry
Cytokines - metabolism
Ligands
Macrophage
Macrophages - metabolism
Microstructured titanium
Surface Properties
Titanium - chemistry
Titanium - pharmacology
Wnt signaling
Wnt Signaling Pathway
Wnt3a
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Summary:Biomaterial characteristics like surface roughness and wettability can determine the phenotype of macrophages following implantation. We have demonstrated that inhibiting Wnt ligand secretion abolishes macrophage polarization in vitro and in vivo; however, the role of canonical Wnt signaling in macrophage activation in response to physical and chemical biomaterial cues is unknown. The aim of this study was to understand whether canonical Wnt signaling affects the response of macrophages to titanium (Ti) surface roughness or wettability in vitro and in vivo. Activating canonical Wnt signaling increased expression of toll-like receptors and interleukin receptors and secreted pro-inflammatory cytokines and reduced anti-inflammatory cytokines on Ti, regardless of surface properties. Inhibiting canonical Wnt signaling reduced pro-inflammatory cytokines on all Ti surfaces and increased anti-inflammatory cytokines on rough or rough-hydrophilic Ti. In vivo, activating canonical Wnt signaling increased total macrophages, pro-inflammatory macrophages, and T cells and decreased anti-inflammatory macrophages on both smooth and rough-hydrophilic implants. Functionally, canonical Wnt activation increases pro-inflammatory macrophage response to cell and cell-extracellular matrix lysates. These results demonstrate that activating canonical Wnt signaling primes macrophages to a pro-inflammatory phenotype that affects their response to Ti implants in vitro and in vivo.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2022.121797