Mechanical Loading Induces NRF2 Nuclear Translocation to Epigenetically Remodel Oxidative Stress Defense in Osteocytes
The mechano-responsiveness of osteocytes is critical for maintaining bone health and associated with a reduced oxidative stress defense, yet the precise molecular mechanisms remain incompletely understood. Here, we address the gap by investigating the epigenetic reprogramming that drives osteocyte r...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-03-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/3/346 |
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| author | Yue Guo Jing Zhang Luyu Gong Na Liu Qiaoqiao Liu Zhaojun Liu Baosheng Guo Jingping Yang |
| author_facet | Yue Guo Jing Zhang Luyu Gong Na Liu Qiaoqiao Liu Zhaojun Liu Baosheng Guo Jingping Yang |
| author_sort | Yue Guo |
| collection | DOAJ |
| description | The mechano-responsiveness of osteocytes is critical for maintaining bone health and associated with a reduced oxidative stress defense, yet the precise molecular mechanisms remain incompletely understood. Here, we address the gap by investigating the epigenetic reprogramming that drives osteocyte responses to mechanical loading. We found overall remodeling of antioxidant response under mechanical loading and identified NRF2, a key transcription factor in oxidative stress response, which plays a vital role in the epigenetic remodeling of osteocytes. The results showed that mechanical loading enhanced NRF2 protein stability, promoted its nuclear translocation, and activated osteocyte-specific transcriptional programs. In contrast, pharmacological stabilization of NRF2 failed to fully replicate these effects, underscoring the unique role of mechanical stimuli in modulating NRF2 activity and antioxidant function. Our findings highlight the potential therapeutic limitations of NRF2-stabilizing drugs and suggest that combining pharmacological approaches with mechanical interventions could offer more effective treatments to maintain oxidative homeostasis. |
| format | Article |
| id | doaj-art-e12d8a8f9fcd487385a3e99837ab8dc6 |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-e12d8a8f9fcd487385a3e99837ab8dc62025-08-20T02:11:21ZengMDPI AGAntioxidants2076-39212025-03-0114334610.3390/antiox14030346Mechanical Loading Induces NRF2 Nuclear Translocation to Epigenetically Remodel Oxidative Stress Defense in OsteocytesYue Guo0Jing Zhang1Luyu Gong2Na Liu3Qiaoqiao Liu4Zhaojun Liu5Baosheng Guo6Jingping Yang7Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, ChinaThe mechano-responsiveness of osteocytes is critical for maintaining bone health and associated with a reduced oxidative stress defense, yet the precise molecular mechanisms remain incompletely understood. Here, we address the gap by investigating the epigenetic reprogramming that drives osteocyte responses to mechanical loading. We found overall remodeling of antioxidant response under mechanical loading and identified NRF2, a key transcription factor in oxidative stress response, which plays a vital role in the epigenetic remodeling of osteocytes. The results showed that mechanical loading enhanced NRF2 protein stability, promoted its nuclear translocation, and activated osteocyte-specific transcriptional programs. In contrast, pharmacological stabilization of NRF2 failed to fully replicate these effects, underscoring the unique role of mechanical stimuli in modulating NRF2 activity and antioxidant function. Our findings highlight the potential therapeutic limitations of NRF2-stabilizing drugs and suggest that combining pharmacological approaches with mechanical interventions could offer more effective treatments to maintain oxidative homeostasis.https://www.mdpi.com/2076-3921/14/3/346osteocytesmechanical loadingNRF2epigenetic remodelingpharmacological modulationoxidative homeostasis |
| spellingShingle | Yue Guo Jing Zhang Luyu Gong Na Liu Qiaoqiao Liu Zhaojun Liu Baosheng Guo Jingping Yang Mechanical Loading Induces NRF2 Nuclear Translocation to Epigenetically Remodel Oxidative Stress Defense in Osteocytes Antioxidants osteocytes mechanical loading NRF2 epigenetic remodeling pharmacological modulation oxidative homeostasis |
| title | Mechanical Loading Induces NRF2 Nuclear Translocation to Epigenetically Remodel Oxidative Stress Defense in Osteocytes |
| title_full | Mechanical Loading Induces NRF2 Nuclear Translocation to Epigenetically Remodel Oxidative Stress Defense in Osteocytes |
| title_fullStr | Mechanical Loading Induces NRF2 Nuclear Translocation to Epigenetically Remodel Oxidative Stress Defense in Osteocytes |
| title_full_unstemmed | Mechanical Loading Induces NRF2 Nuclear Translocation to Epigenetically Remodel Oxidative Stress Defense in Osteocytes |
| title_short | Mechanical Loading Induces NRF2 Nuclear Translocation to Epigenetically Remodel Oxidative Stress Defense in Osteocytes |
| title_sort | mechanical loading induces nrf2 nuclear translocation to epigenetically remodel oxidative stress defense in osteocytes |
| topic | osteocytes mechanical loading NRF2 epigenetic remodeling pharmacological modulation oxidative homeostasis |
| url | https://www.mdpi.com/2076-3921/14/3/346 |
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