NOD2 negatively regulated titanium particle-induced osteolysis in mice
NOD2 negatively regulated titanium particle-induced osteolysis in mice
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NOD2 负向调节钛颗粒诱导的小鼠骨溶解
DOI：
10.1039/c9bm00306a
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发表时间：
2019-07-01
影响因子：
6.6
通讯作者：
Ding, Yue
中科院分区：
文献类型：
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作者：
Li, Shixun;Qiu, Junxiong;Ding, Yue
对于接受全关节置换术（TJR）的患者，其中一种并发症无菌性松动可能导致严重的后果，如翻修手术。在早期的研究中，模式识别受体（PRRs）在识别假体的磨损颗粒和启动炎症反应中起着至关重要的作用。在本研究中，我们旨在阐明PRRs之一的核苷酸结合和oligomerization domain containing protein 2 （NOD2）在体内和体外巨噬细胞诱导的无菌性松动中的作用。在20例接受原发性或翻修性全髋关节置换术（THR）的患者中观察到NOD2和TNFa的高表达。在RAW264.7细胞和CRISPR-Cas9 NOD2敲除小鼠中观察NOD2对炎症通路激活的影响。磨损颗粒刺激的巨噬细胞中NOD2、NF-kappa B通路、MAPK通路和促炎细胞因子tnf - α表达上调。否则，抑制NOD2进一步上调NOD2、NF-kappa B通路、MAPK通路和tnf - α的表达。在小鼠模型中，敲低NOD2基因可增强钛颗粒诱导的颅骨骨溶解。综上所述，我们的研究表明NOD2在体外和体内均对钛颗粒诱导的骨溶解具有负向作用。
For patients undergoing total joint replacement (TJR), one of the complications, aseptic loosening, could cause serious consequences, such as revision surgery. In early research, pattern recognition receptors (PRRs) were reported to play vital roles in recognizing wear particles from the prosthesis and initiating an inflammation response. In this research, we aimed to clarify the role of nucleotide-binding and oligomerization domain containing protein 2 (NOD2), one of the PRRs, in macrophage-induced aseptic loosening in vivo and in vitro. High expressions of NOD2 and TNFa were observed from twenty patients who underwent primary or revision total hip replacements (THR). The effect of NOD2 on the activation of inflammation pathways was observed in RAW264.7 cells and CRISPR-Cas9 NOD2-knockout mice. The expressions of NOD2, the NF-kappa B pathway, the MAPK pathway and proinflammatory cytokine TNF-alpha in macrophages stimulated by wear particles were up-regulated. Otherwise, inhibition of NOD2 further upregulated the expressions of NOD2, the NF-kappa B pathway, the MAPK pathway and TNF-alpha. Knockdown of the NOD2 gene enhanced the cranial osteolysis induced by titanium particles in a mouse model. In conclusion, our study demonstrated that NOD2 plays a negative role in osteolysis induced by titanium particles in vitro and in vivo.