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

Canonical Wnt signaling enhances pro-inflammatory response to titanium by macrophages.
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DOI:
10.1016/j.biomaterials.2022.121797
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发表时间:
2022-10
期刊:
影响因子:
14
通讯作者:
--
中科院分区:
工程技术1区
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--
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生物材料的特性,如表面粗糙度和润湿性,可以决定植入后的巨噬细胞的表型。我们已经证明,抑制Wnt配体分泌废除巨噬细胞极化在体外和体内,然而,经典的Wnt信号在巨噬细胞活化中的作用,响应物理和化学生物材料的线索是未知的。本研究的目的是了解经典Wnt信号是否影响巨噬细胞对钛(Ti)表面粗糙度或润湿性的反应。激活经典Wnt信号传导增加了Toll样受体和白细胞介素受体的表达,并分泌促炎细胞因子,减少了Ti上的抗炎细胞因子,而与表面性质无关。抑制经典Wnt信号传导减少了所有Ti表面上的促炎细胞因子,并增加了粗糙或粗糙亲水性Ti上的抗炎细胞因子。在体内,激活经典Wnt信号增加了光滑和粗糙亲水性植入物上的总巨噬细胞、促炎性巨噬细胞和T细胞,并减少了抗炎性巨噬细胞。在功能上,典型的Wnt激活增加了对细胞和细胞-细胞外基质裂解物的促炎性巨噬细胞应答。这些结果表明,激活经典Wnt信号转导可使巨噬细胞产生促炎表型,从而影响其对体外和体内钛植入物的反应。
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.
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