دورية أكاديمية
Optineurin regulates NRF2-mediated antioxidant response in a mouse model of Paget’s disease of bone
| العنوان: | Optineurin regulates NRF2-mediated antioxidant response in a mouse model of Paget’s disease of bone |
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| المؤلفون: | Hu X, Wong S.-W, Liang K, Wu T.-H, Wang S, Wang L, Liu J, Yamauchi M, Foster B.L, Ting J.P.-Y, Zhao B, Tseng H.C, Ko C.-C |
| المصدر: | Science Advances, 9(4) |
| بيانات النشر: | American Association for the Advancement of Science |
| سنة النشر: | 2023 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | Mammals, Animals, Paget bone disease, Skeletal system, Osteoclastogenesis, Bone disease, Elderly people, NF-E2-Related Factor 2, Kelch-Like ECH-Associated Protein 1, Mice, Degenerative disease, bone development, Related factors, animal, transcription factor Nrf2, Anti-oxidant response, Age-related, Nuclear factors, Mice models, Osteitis Deformans, Neurodegenerative diseases, Antioxidants, kelch like ECH associated protein 1, Osteogenesis, metabolism, mouse, antioxidant, Bone |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/gkpy-fw88Test; https://cdr.lib.unc.edu/downloads/g732dm787?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/g732dm787Test |
| DOI: | 10.17615/gkpy-fw88 |
| الإتاحة: | https://doi.org/10.17615/gkpy-fw88Test https://cdr.lib.unc.edu/downloads/g732dm787?file=thumbnailTest https://cdr.lib.unc.edu/downloads/g732dm787Test |
| رقم الانضمام: | edsbas.F5A95BE2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/gkpy-fw88 |
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