例如:"lncRNA", "apoptosis", "WRKY"

The USP14-NLRC5 pathway inhibits titanium particle-induced osteolysis in mice by suppressing NF-κB and PI3K/AKT activities.

J Biol Chem. 2020 May 15;295(20):7018-7032. Epub 2020 Apr 09
Guibin Fang 1 , Yuan Fu 1 , Shixun Li 1 , Junxiong Qiu 1 , Manyuan Kuang 1 , Sipeng Lin 1 , Changchuan Li 1 , Yue Ding 2
Guibin Fang 1 , Yuan Fu 1 , Shixun Li 1 , Junxiong Qiu 1 , Manyuan Kuang 1 , Sipeng Lin 1 , Changchuan Li 1 , Yue Ding 2
+ et al

[No authors listed]

Author information
  • 1 Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
  • 2 Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China dingyue@mail.sysu.edu.cn.

摘要


Total hip arthroplasty (THA) is a widely-used surgical intervention for treating patients with end-stage degenerative and inflammatory osteoarthropathy. However, wear particles from the artificial titanium joint can induce osteolysis, limiting the long-term survivorship of THA. Monocyte/macrophage lineage cells are the key players in the response to wear particles, and the proinflammatory NF-κB and phosphoinositide 3-kinase (PI3K)-AKT Ser/Thr kinase (AKT)-signaling pathways have been shown to be the most important contributors to wear particle-induced osteolysis. In contrast, ubiquitin-specific protease 14 (USP14) specifically removes the polyubiquitin chains from the nucleotide-binding and oligomerization domain (NOD)-like receptor family Caspase recruitment domain (CARD)-containing 5 (NLRC5) and thereby enhances the NLRC5-mediated inhibition of NF-κB signaling. In this study, we aimed to clarify the role of the USP14-NLRC5 pathway in wear particle-induced osteolysis in vitro and in vivo We found that NLRC5 or USP14 overexpression inhibits titanium particle-induced proinflammatory tumor necrosis factor α (TNFα) production and NF-κB pathway activation, and it also decreases M1 macrophage polarization and PI3K/AKT pathway activation. Of note, NLRC5 and USP14 overexpression attenuated titanium particle-induced cranial osteolysis in mice. In conclusion, the findings of our study indicate that the USP14-NLRC5 pathway inhibits titanium particle-induced osteolysis by suppressing the NF-κB and PI3K/AKT pathways both in vitro and in vivo.

KEYWORDS: NF-κB, NLRC5, USP14, cytokine, macrophage, osteoclast, total hip arthroplasty, tumor necrosis factor (TNF), wear particles