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NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway.
Wang, Wei; Liang, Xiaolong; Liu, Xin; Bai, Jiaxiang; Zhang, Wei; Li, Wenming; Wang, Tianhao; Li, Meng; Wu, Zerui; Chen, Liang; Yang, Huilin; Gu, Ye; Tao, Yunxia; Zhou, Jun; Wang, Huaiyu; Geng, Dechun.
Affiliation
  • Wang W; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Liang X; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Liu X; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Bai J; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Zhang W; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Li W; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Wang T; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Li M; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Wu Z; Department of Orthopedic Surgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, 230001, Anhui, China.
  • Chen L; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Yang H; Department of Orthopedic Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China.
  • Gu Y; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Tao Y; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Zhou J; Department of Orthopedics, Changshu Hospital Affiliated to Soochow University, First People's Hospital of Changshu City, Changshu, China. edwinguye@126.com.
  • Wang H; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China. taoyx8493@163.com.
  • Geng D; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China. zhou.jun.roy@hotmail.com.
J Nanobiotechnology ; 20(1): 241, 2022 May 23.
Article in En | MEDLINE | ID: mdl-35606794
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteolysis / Nanoparticles Limits: Animals Language: En Journal: J Nanobiotechnology Year: 2022 Type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteolysis / Nanoparticles Limits: Animals Language: En Journal: J Nanobiotechnology Year: 2022 Type: Article Affiliation country: China