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CB2 regulates oxidative stress and osteoclastogenesis through NOX1-dependent signaling pathway in titanium particle-induced osteolysis

Authors :
Huaqiang Tao
Xueyan Li
Miao Chu
Qiufei Wang
Ping Li
Qibin Han
Kai Chen
Pengfei Zhu
Yuefeng Hao
Xing Yang
Dechun Geng
Ye Gu
Source :
Cell Death Discovery, Vol 9, Iss 1, Pp 1-12 (2023)
Publication Year :
2023
Publisher :
Nature Publishing Group, 2023.

Abstract

Abstract Periprosthetic osteolysis (PPO) induced by wear particles at the interface between the prosthesis and bone is a crucial issue of periprosthetic bone loss and implant failure. After wear and tear, granular material accumulates around the joint prosthesis, causing a chronic inflammatory response, progressive osteoclast activation and eventual loosening of the prosthesis. Although many studies have been conducted to address bone loss after joint replacement surgeries, they have not fully addressed these issues. Focusing on osteoclast activation induced by particles has important theoretical implications. Cannabinoid type II receptor (CB2) is a seven-transmembrane receptor that is predominantly distributed in the human immune system and has been revealed to be highly expressed in bone-associated cells. Previous studies have shown that modulation of CB2 has a positive effect on bone metabolism. However, the exact mechanism has not yet been elucidated. In our experiments, we found that NOX1-mediated ROS accumulation was involved in titanium particle-stimulated osteoclast differentiation. Furthermore, we confirmed that CB2 blockade alleviated titanium particle-stimulated osteoclast activation by inhibiting the NOX1-mediated oxidative stress pathway. In animal experiments, downregulation of CB2 alleviated the occurrence of titanium particle-induced cranial osteolysis by inhibiting osteoclasts and scavenging intracellular ROS. Collectively, our results suggest that CB2 blockade may be an attractive and promising therapeutic scheme for particle-stimulated osteoclast differentiation and preventing PPO.

Details

Language :
English
ISSN :
20587716
Volume :
9
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Cell Death Discovery
Publication Type :
Academic Journal
Accession number :
edsdoj.f96ab337738b4519803dd8d6b83049fc
Document Type :
article
Full Text :
https://doi.org/10.1038/s41420-023-01761-y