Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP–RIPK1–NF-κB axis and influencing autophagy
Abstract Background Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma,...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-05086-x |
| _version_ | 1797259075829891072 |
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| author | Chunran Pan Fan Lu Xiaoxia Hao Xiaofeng Deng Jiawei Liu Kai Sun Wenjie Hou Xingru Shang Ruimin Chi Fengjing Guo Tao Xu |
| author_facet | Chunran Pan Fan Lu Xiaoxia Hao Xiaofeng Deng Jiawei Liu Kai Sun Wenjie Hou Xingru Shang Ruimin Chi Fengjing Guo Tao Xu |
| author_sort | Chunran Pan |
| collection | DOAJ |
| description | Abstract Background Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma, obesity, and age. Unfortunately, due to limited understanding of its pathological mechanism, there are currently no effective drugs or treatments to suspend the progression of osteoarthritis. In recent years, some studies found that low-intensity pulsed ultrasound (LIPUS) may have a positive effect on osteoarthritis. Nonetheless, the exact mechanism by which LIPUS affects osteoarthritis remains unknown. It is valuable to explore the specific mechanism of LIPUS in the treatment of OA. Methods In this study, we validated the potential therapeutic effect of LIPUS on osteoarthritis by regulating the YAP–RIPK1–NF-κB axis at both cellular and animal levels. To verify the effect of YAP on OA, the expression of YAP was knocked down or overexpressed by siRNA and plasmid in chondrocytes and adeno-associated virus was injected into the knee joint of rats. The effect of LIPUS was investigated in inflammation chondrocytes induced by IL-1β and in the post-traumatic OA model. Results In this study, we observed that YAP plays an important role in the development of osteoarthritis and knocking down of YAP significantly inhibited the inflammation and alleviated cartilage degeneration. We also demonstrated that the expression of YAP was increased in osteoarthritis chondrocytes and YAP could interact with RIPK1, thereby regulating the NF-κB signal pathway and influencing inflammation. Moreover, we also discovered that LIPUS decreased the expression of YAP by restoring the impaired autophagy capacity and inhibiting the binding between YAP and RIPK1, thereby delaying the progression of osteoarthritis. Animal experiment showed that LIPUS could inhibit cartilage degeneration and alleviate the progression of OA. Conclusions These results showed that LIPUS is effective in inhibiting inflammation and cartilage degeneration and alleviate the progression of OA. As a result, our results provide new insight of mechanism by which LIPUS delays the development of osteoarthritis, offering a novel therapeutic regimen for osteoarthritis. |
| first_indexed | 2024-04-24T23:03:40Z |
| format | Article |
| id | doaj.art-6a29278c40f94f7b92a70022f1aa18cf |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-24T23:03:40Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-6a29278c40f94f7b92a70022f1aa18cf2024-03-17T12:36:37ZengBMCJournal of Translational Medicine1479-58762024-03-0122112010.1186/s12967-024-05086-xLow-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP–RIPK1–NF-κB axis and influencing autophagyChunran Pan0Fan Lu1Xiaoxia Hao2Xiaofeng Deng3Jiawei Liu4Kai Sun5Wenjie Hou6Xingru Shang7Ruimin Chi8Fengjing Guo9Tao Xu10Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma, obesity, and age. Unfortunately, due to limited understanding of its pathological mechanism, there are currently no effective drugs or treatments to suspend the progression of osteoarthritis. In recent years, some studies found that low-intensity pulsed ultrasound (LIPUS) may have a positive effect on osteoarthritis. Nonetheless, the exact mechanism by which LIPUS affects osteoarthritis remains unknown. It is valuable to explore the specific mechanism of LIPUS in the treatment of OA. Methods In this study, we validated the potential therapeutic effect of LIPUS on osteoarthritis by regulating the YAP–RIPK1–NF-κB axis at both cellular and animal levels. To verify the effect of YAP on OA, the expression of YAP was knocked down or overexpressed by siRNA and plasmid in chondrocytes and adeno-associated virus was injected into the knee joint of rats. The effect of LIPUS was investigated in inflammation chondrocytes induced by IL-1β and in the post-traumatic OA model. Results In this study, we observed that YAP plays an important role in the development of osteoarthritis and knocking down of YAP significantly inhibited the inflammation and alleviated cartilage degeneration. We also demonstrated that the expression of YAP was increased in osteoarthritis chondrocytes and YAP could interact with RIPK1, thereby regulating the NF-κB signal pathway and influencing inflammation. Moreover, we also discovered that LIPUS decreased the expression of YAP by restoring the impaired autophagy capacity and inhibiting the binding between YAP and RIPK1, thereby delaying the progression of osteoarthritis. Animal experiment showed that LIPUS could inhibit cartilage degeneration and alleviate the progression of OA. Conclusions These results showed that LIPUS is effective in inhibiting inflammation and cartilage degeneration and alleviate the progression of OA. As a result, our results provide new insight of mechanism by which LIPUS delays the development of osteoarthritis, offering a novel therapeutic regimen for osteoarthritis.https://doi.org/10.1186/s12967-024-05086-xOsteoarthritisChondrocyteAutophagyYAPLIPUS |
| spellingShingle | Chunran Pan Fan Lu Xiaoxia Hao Xiaofeng Deng Jiawei Liu Kai Sun Wenjie Hou Xingru Shang Ruimin Chi Fengjing Guo Tao Xu Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP–RIPK1–NF-κB axis and influencing autophagy Journal of Translational Medicine Osteoarthritis Chondrocyte Autophagy YAP LIPUS |
| title | Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP–RIPK1–NF-κB axis and influencing autophagy |
| title_full | Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP–RIPK1–NF-κB axis and influencing autophagy |
| title_fullStr | Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP–RIPK1–NF-κB axis and influencing autophagy |
| title_full_unstemmed | Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP–RIPK1–NF-κB axis and influencing autophagy |
| title_short | Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP–RIPK1–NF-κB axis and influencing autophagy |
| title_sort | low intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the yap ripk1 nf κb axis and influencing autophagy |
| topic | Osteoarthritis Chondrocyte Autophagy YAP LIPUS |
| url | https://doi.org/10.1186/s12967-024-05086-x |
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