视神经肽
KEAP1型
氧化应激
蛋白质数据库
佩吉特骨病
疾病
平衡
细胞生物学
活性氧
医学
生物
免疫学
癌症研究
转录因子
内科学
肌萎缩侧索硬化
生物化学
基因
作者
Xinran Hu,Sing‐Wai Wong,Kaixin Liang,Tai-Hsien Wu,Sheng Wang,Lufei Wang,Jie Liu,Mitsuo Yamauchi,Brian L. Foster,Jenny P.-Y. Ting,Baohong Zhao,Henry Tseng,Ching‐Chang Ko
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-01-27
卷期号:9 (4)
被引量:4
标识
DOI:10.1126/sciadv.ade6998
摘要
Degenerative diseases affecting the nervous and skeletal systems affect the health of millions of elderly people. Optineurin (OPTN) has been associated with numerous neurodegenerative diseases and Paget's disease of bone (PDB), a degenerative bone disease initiated by hyperactive osteoclastogenesis. In this study, we found age-related increase in OPTN and nuclear factor E2-related factor 2 (NRF2) in vivo. At the molecular level, OPTN could directly interact with both NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) for up-regulating antioxidant response. At the cellular level, deletion of OPTN resulted in increased intracellular reactive oxygen species and increased osteoclastogenic potential. At the tissue level, deletion of OPTN resulted in substantially increased oxidative stress derived from leukocytes that further stimulate osteoclastogenesis. Last, curcumin attenuated hyperactive osteoclastogenesis induced by OPTN deficiency in aged mice. Collectively, our findings reveal an OPTN-NRF2 axis maintaining bone homeostasis and suggest that antioxidants have therapeutic potential for PDB.
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