首页
内分泌科 神经内科 心血管内科 消化内科 风湿免疫科 血液科 肾内科 呼吸内科 神经外科 心脏外科 胸部外科 普通外科 肝胆外科 烧伤外科 整形外科 泌尿外科 妇产科 儿科 皮肤性病科 感染科 眼科 急诊科 精神科 口腔科 肿瘤科 骨科 耳鼻咽喉头颈外科
疾病 检查 药品 操作 文献 专题 路径 法规 量表

您的账号已在其他设备登录，您当前账号已强迫下线，
如非您本人操作，建议您在会员中心进行密码修改

确定
首页 > Free radical biology & medicine > Nrf2 deficiency induces oxidative stress and promotes RANKL-induced osteoclast differe...
Nrf2 deficiency induces oxidative stress and promotes RANKL-induced osteoclast differentiation.
LinkOut
收藏 | 浏览116

Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that regulates the expression of a variety of antioxidant and detoxification genes through an antioxidant-response element. Nrf2 has been shown to protect several types of cells against the acute and chronic injury that accompanies oxidative stress, but its role in osteoclasts remains unclear. In this study, we investigated the role of Nrf2 in osteoclast (OC) differentiation, a process in which reactive oxygen species (ROS) are generated and then participate, using Nrf2-knockout mice. Receptor activator of nuclear factor κB ligand (RANKL)-induced OC differentiation, actin ring formation, and osteoclastic bone resorption were substantially promoted in Nrf2-deficient OC precursor cells compared to wild-type cells. Under both unstimulated and RANKL-stimulated conditions, Nrf2 loss led to an increase in the intracellular ROS level and the oxidized-to-reduced glutathione ratio and a defect in the production of numerous antioxidant enzymes and glutathione. Moreover, pretreatment with N-acetylcysteine or diphenyleneiodonium significantly reduced the OC differentiation and decreased the intracellular ROS level in both Nrf2-deficient and wild-type cells. Pretreatment with sulforaphane and curcumin also inhibited the OC differentiation by activating Nrf2 in part. Nrf2 deficiency promoted the RANKL-induced activation of mitogen-activated protein kinases, including c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38; the induction of c-Fos; and the consequent induction of nuclear factor of activated T cells, cytoplasmic 1, a pivotal determinant of OC differentiation. Our results suggest that Nrf2 probably inhibits RANKL-induced OC differentiation by regulating the cellular redox status by controlling the expression of oxidative response genes, findings that might form the basis of a new strategy for treating inflammatory bone diseases.

作者：Seungha, Hyeon；Hyojung, Lee；Yoohee, Yang；Woojin, Jeong

来源：Free radical biology & medicine 2013 年 65卷

循证诊断
知识库介绍

临床诊疗知识库该平台旨在解决临床医护人员在学习、工作中对医学信息的需求，方便快速、便捷的获取实用的医学信息，辅助临床决策参考。该库包含疾病、药品、检查、指南规范、病例文献及循证文献等多种丰富权威的临床资源。

详细介绍
热门关注
免责声明：本知识库提供的有关内容等信息仅供学习参考，不代替医生的诊断和医嘱。

Nrf2 deficiency induces oxidative stress and promotes RANKL-induced osteoclast differentiation.
收藏
| 浏览：116
作者：
Seungha, Hyeon；Hyojung, Lee；Yoohee, Yang；Woojin, Jeong
来源：
Free radical biology & medicine 2013 年 65卷
标签：
AP-1 ARE BMM DPI ERK FBS Free radicals GSH GSSG JNK Keap1 Kelch-like ECH-associated protein 1 M-CSF MAPK MAPK phosphatase MEM MKP Mitogen-activated protein kinases N-acetylcysteine NAC NAD(P)H:quinone oxidoreductase 1 NADPH NADPH oxidase NF-κB NFATc1 NQO1 Nox Nrf2 OC OC differentiation PBS Prx RANKL ROS Reactive oxygen species Redox regulation SOD Srx TNF TNF receptor-associated factor TRAF TRAP TRAP(+) MNC TRAP-positive multinucleated cell Trx Trx reductase TrxR activator protein-1 antioxidant response element bone marrow-derived macrophage c-Jun N-terminal kinase diphenyleneiodonium extracellular signal-regulated kinase fetal bovine serum glutathione macrophage colony-stimulating factor minimal essential medium mitogen-activated protein kinase nicotinamide adenine dinucleotide phosphate nuclear factor of activated T cells, cytoplasmic 1 nuclear factor-erythroid 2-related factor 2 nuclear factor-κB osteoclast oxidized GSH peroxiredoxin phosphate-buffered saline reactive oxygen species receptor activator of NF-κB ligand sulfiredoxin superoxide dismutase tartrate-resistant acid phosphatase thioredoxin tumor necrosis factor
Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that regulates the expression of a variety of antioxidant and detoxification genes through an antioxidant-response element. Nrf2 has been shown to protect several types of cells against the acute and chronic injury that accompanies oxidative stress, but its role in osteoclasts remains unclear. In this study, we investigated the role of Nrf2 in osteoclast (OC) differentiation, a process in which reactive oxygen species (ROS) are generated and then participate, using Nrf2-knockout mice. Receptor activator of nuclear factor κB ligand (RANKL)-induced OC differentiation, actin ring formation, and osteoclastic bone resorption were substantially promoted in Nrf2-deficient OC precursor cells compared to wild-type cells. Under both unstimulated and RANKL-stimulated conditions, Nrf2 loss led to an increase in the intracellular ROS level and the oxidized-to-reduced glutathione ratio and a defect in the production of numerous antioxidant enzymes and glutathione. Moreover, pretreatment with N-acetylcysteine or diphenyleneiodonium significantly reduced the OC differentiation and decreased the intracellular ROS level in both Nrf2-deficient and wild-type cells. Pretreatment with sulforaphane and curcumin also inhibited the OC differentiation by activating Nrf2 in part. Nrf2 deficiency promoted the RANKL-induced activation of mitogen-activated protein kinases, including c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38; the induction of c-Fos; and the consequent induction of nuclear factor of activated T cells, cytoplasmic 1, a pivotal determinant of OC differentiation. Our results suggest that Nrf2 probably inhibits RANKL-induced OC differentiation by regulating the cellular redox status by controlling the expression of oxidative response genes, findings that might form the basis of a new strategy for treating inflammatory bone diseases.

关于我们 产品特色 专家团队

免责声明：本知识库提供的有关疾病、症状、检查、药品、指南规范、循证文献和病例文献等信息仅供医生学习参考。

2015 北京万方数据股份有限公司 互联网药品信息服务资格证书号：(京)-经营性-2011-0017 京ICP证010071号