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NOD2 negatively regulated titanium particle-induced osteolysis in mice

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Abstract

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 TNFα 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-κB pathway, the MAPK pathway and proinflammatory cytokine TNF-α in macrophages stimulated by wear particles were up-regulated. Otherwise, inhibition of NOD2 further up-regulated the expressions of NOD2, the NF-κB pathway, the MAPK pathway and TNF-α. 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.

Graphical abstract: NOD2 negatively regulated titanium particle-induced osteolysis in mice

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Publication details

The article was received on 25 Feb 2019, accepted on 12 Apr 2019 and first published on 08 May 2019


Article type: Paper
DOI: 10.1039/C9BM00306A
Biomater. Sci., 2019, Advance Article
  • Open access: Creative Commons BY-NC license
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    NOD2 negatively regulated titanium particle-induced osteolysis in mice

    S. Li, J. Qiu, L. Qin, P. Peng, C. Li, J. Mao, G. Fang, Z. Chen, S. Lin, Y. Fu, W. Cai and Y. Ding, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C9BM00306A

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