1. Academic Validation
  2. NOD2 negatively regulated titanium particle-induced osteolysis in mice

NOD2 negatively regulated titanium particle-induced osteolysis in mice

  • Biomater Sci. 2019 Jul 1;7(7):2702-2715. doi: 10.1039/c9bm00306a.
Shixun Li 1 Junxiong Qiu 1 Ling Qin 2 Peng Peng 1 Changchuan Li 1 Jiaji Mao 3 Guibin Fang 1 Zhong Chen 1 Sipeng Lin 1 Yuan Fu 1 Weibin Cai 4 Yue Ding 1
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. dingyue@mail.sysu.edu.cn.
  • 2 Musculoskeletal Research Laboratory Department of Orthopaedics & Taumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong, SAR, PR China.
  • 3 Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
  • 4 Guangdong Engineering & Technology Research Center for Disease-Model Animals, Laboratory Animal Center and Department of Biochemistry, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou 510080, China. caiwb@mail.sysu.edu.cn.
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.

Figures
Products