NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway

被引：14

作者：

Wang, Wei ^{[1
]}

Liang, Xiaolong ^{[1
]}

Liu, Xin ^{[1
]}

Bai, Jiaxiang ^{[1
]}

Zhang, Wei ^{[1
]}

Li, Wenming ^{[1
]}

Wang, Tianhao ^{[1
]}

Li, Meng ^{[1
,2
]}

Wu, Zerui ^{[1
,3
]}

Chen, Liang ^{[1
]}

Yang, Huilin ^{[1
]}

Gu, Ye ^{[4
]}

Tao, Yunxia ^{[1
]}

Zhou, Jun ^{[1
]}

Wang, Huaiyu ^{[5
]}

Geng, Dechun ^{[1
,4
]}

机构：

[1] Soochow Univ, Dept Orthoped, Affiliated Hosp 1, Suzhou 215006, Jiangsu, Peoples R China

[2] Univ Sci & Technol China, Dept Orthoped Surg, Affiliated Hosp 1, Hefei 230001, Anhui, Peoples R China

[3] Xuzhou Med Univ, Dept Orthoped Surg, Affiliated Hosp, Xuzhou 221002, Jiangsu, Peoples R China

[4] Soochow Univ, Peoples Hosp Changshu City 1, Dept Orthoped, Changshu Hosp, Changshu, Peoples R China

[5] Chinese Acad Sci, Ctr Human Tissues & Organs Degenerat, Shenzhen Inst Adv Technol, Shenzhen 518055, Peoples R China

来源：

JOURNAL OF NANOBIOTECHNOLOGY | 2022年 / 20卷 / 01期

关键词：

Periprosthetic osteolysis; Titanium nanoparticles; Osteoclastogenesis; NOX4; Nrf2; RANKL-INDUCED OSTEOCLASTOGENESIS; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; OSTEOLYSIS; ROS; ARTHROPLASTY; POLYETHYLENE; PARTICLES;

D O I：

10.1186/s12951-022-01413-w

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Periprosthetic osteolysis (PPO) triggered by wear particles is the most severe complication of total joint replacement (TJR) surgeries, representing the major cause of implant failure, which is public health concern worldwide. Previous studies have confirmed the specialized role of osteoclast-induced progressive bone destruction in the progression of PPO. Additionally, the reactive oxygen species (ROS) induced by wear particles can promote excessive osteoclastogenesis and bone resorption. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), a cellular enzyme, is considered to be responsible for the production of ROS and the formation of mature osteoclasts. However, NOX4 involvement in PPO has not yet been elucidated. Therefore, we investigated the mechanism by which NOX4 regulates osteoclast differentiation and the therapeutic effects on titanium nanoparticle-induced bone destruction. We found that NOX4 blockade suppressed osteoclastogenesis and enhanced the scavenging of intracellular ROS. Our rescue experiment revealed that nuclear factor-erythroid 2-related factor 2 (Nrf2) silencing reversed the effects of NOX4 blockade on ROS production and osteoclast differentiation. In addition, we found increased expression levels of NOX4 in PPO tissues, while NOX4 inhibition in vivo exerted protective effects on titanium nanoparticle-induced osteolysis through antiosteoclastic and antioxidant effects. Collectively, these findings suggested that NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway and that NOX4 blockade may be an attractive therapeutic approach for preventing PPO.

引用

页数：15

共 62 条

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