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钛和氧化锆颗粒诱导培养的巨噬细胞产生促炎基因表达及体内骨溶解、炎症性痛觉过敏和水肿。

Titanium and zirconia particle-induced pro-inflammatory gene expression in cultured macrophages and osteolysis, inflammatory hyperalgesia and edema in vivo.

机构信息

Laboratory of Applied Immunology, Department of Anatomy, Cell Biology, Physiology and Biophysics, Institute of Biology, IB/UNICAMP, Campinas, Sao Paulo, Brazil.

Laboratory of Pain Physiology, Department of Physiology, Federal University of Parana, Curitiba, Parana, Brazil.

出版信息

Life Sci. 2014 Mar 3;97(2):96-106. doi: 10.1016/j.lfs.2013.11.008. Epub 2013 Nov 16.

DOI:10.1016/j.lfs.2013.11.008
PMID:24252315
Abstract

AIMS

The biological reaction to wear debris is critical to the osteolysis underlying aseptic loosening of joint prosthetic implants. In an attempt to reduce aseptic loosening, ceramics have been introduced. This study was designed to evaluate, compare and correlate the expression of Toll-like receptors (TLRs), their intracellular adaptors and proinflammatory cytokines in cultured macrophages challenged with titanium or zirconia particles, as well as particle-induced osteolysis in calvaria and hyperalgesia and edema in hind paw.

MAIN METHODS

TLRs and their adaptors were evaluated at the mRNA level by RT-PCR, and cytokine expression was evaluated at the mRNA and protein levels. Osteolysis and hyperalgesia and edema were evaluated in vivo, in calvaria and hind paw, respectively.

KEY FINDINGS

Cultured macrophages challenged with zirconia or titanium particles expressed increased mRNA for TLRs 2, 3, 4 and 9, and their adaptors MyD88, TRIF and NF-κB and cytokines TNF-α, IL-1β and IL-6, which were also increased at protein level. Quantitative differences are evident and, in general, zirconia particle-induced pro-inflammatory gene expression was lower than that induced by titanium particles. In in vivo experiments, exposition to titanium or zirconia particles induced osteolysis in calvaria and hyperalgesia and edema in hind paw; however those induced by zirconia particles were significantly lower. There is a strong and positive correlation between the expressions of mRNA for TLR4, NF-κB, TNF-α, IL-1β and IL-6.

SIGNIFICANCE

Collectively, our data suggest that zirconia ceramic particles are less bioactive than titanium particles.

摘要

目的

磨损颗粒引起的生物学反应对关节假体植入物无菌性松动所导致的骨溶解至关重要。为了降低无菌性松动的风险,已经引入了陶瓷材料。本研究旨在评估、比较和关联培养的巨噬细胞受到钛或氧化锆颗粒刺激后 Toll 样受体 (TLR)、其细胞内衔接蛋白和促炎细胞因子的表达,以及颗粒诱导的颅骨骨溶解、后爪痛觉过敏和水肿。

主要方法

通过 RT-PCR 评估 TLR 及其衔接蛋白的 mRNA 表达,通过 mRNA 和蛋白质水平评估细胞因子表达。在体内,分别在颅骨和后爪评估骨溶解、痛觉过敏和水肿。

主要发现

用氧化锆或钛颗粒刺激的培养巨噬细胞表达增加的 TLRs 2、3、4 和 9,及其衔接蛋白 MyD88、TRIF 和 NF-κB 和细胞因子 TNF-α、IL-1β 和 IL-6,蛋白质水平也增加。定量差异明显,一般来说,氧化锆颗粒诱导的促炎基因表达低于钛颗粒。在体内实验中,钛或氧化锆颗粒暴露导致颅骨骨溶解、后爪痛觉过敏和水肿;然而,氧化锆颗粒诱导的这些变化显著较低。TLR4、NF-κB、TNF-α、IL-1β 和 IL-6 的 mRNA 表达之间存在强烈的正相关。

意义

总的来说,我们的数据表明氧化锆陶瓷颗粒的生物活性低于钛颗粒。

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