Fasting activates optineurin-mediated mitophagy in chondrocytes to protect against osteoarthritis
Abstract Mitochondrial homeostasis plays a crucial role in the pathogenesis of osteoarthritis (OA), a chronic musculoskeletal disorder characterized by articular cartilage degeneration and chondrocyte apoptosis. However, molecular mechanisms underlying the association between mitophagy and OA remain...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07541-x |
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| author | Min-Na Zhang Ran Duan Gui-Hong Chen Mei-Jun Chen Chun-Gu Hong Xin Wang Zhi-Lin Pang Chun-Yuan Chen Hua-Feng Liu Da Zhong Hui Xie Wen-Bao Hu Zheng-Zhao Liu |
| author_facet | Min-Na Zhang Ran Duan Gui-Hong Chen Mei-Jun Chen Chun-Gu Hong Xin Wang Zhi-Lin Pang Chun-Yuan Chen Hua-Feng Liu Da Zhong Hui Xie Wen-Bao Hu Zheng-Zhao Liu |
| author_sort | Min-Na Zhang |
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| description | Abstract Mitochondrial homeostasis plays a crucial role in the pathogenesis of osteoarthritis (OA), a chronic musculoskeletal disorder characterized by articular cartilage degeneration and chondrocyte apoptosis. However, molecular mechanisms underlying the association between mitophagy and OA remain unclear. Here, we aimed to investigate the role of the autophagy receptor protein optineurin (OPTN) in OA, and explore the effects of dietary intervention on OA symptoms and its relationship with OPTN-mediated mitophagy. Our findings showed the downregulation of OPTN in patients with OA. Using an Optn-knockout mouse model, we demonstrated that OPTN deficiency leads to impaired mitophagy, resulting in the accumulation of damaged mitochondria, increased production of reactive oxygen species, and chondrocyte apoptosis. Furthermore, fasting prevented OA progression by activating OPTN-mediated mitophagy and maintaining mitochondrial homeostasis in mice. The present study revealed a novel mechanism by which OPTN-mediated mitophagy influences chondrocytes and the OA phenotype in Optn-knockout mice, suggesting that OPTN-mediated mitophagy plays a crucial role in OA development and progression. This study provides new insights into the pathogenesis of OA and offers a potential avenue for the development of novel drugs targeting OPTN to mitigate OA progression. |
| format | Article |
| id | doaj-art-9036208b30194f3694a18182eea4a522 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-9036208b30194f3694a18182eea4a5222025-01-19T12:35:15ZengNature PortfolioCommunications Biology2399-36422025-01-018111210.1038/s42003-025-07541-xFasting activates optineurin-mediated mitophagy in chondrocytes to protect against osteoarthritisMin-Na Zhang0Ran Duan1Gui-Hong Chen2Mei-Jun Chen3Chun-Gu Hong4Xin Wang5Zhi-Lin Pang6Chun-Yuan Chen7Hua-Feng Liu8Da Zhong9Hui Xie10Wen-Bao Hu11Zheng-Zhao Liu12Department of Sports Medicine, Xiangya Hospital, Central South UniversityThe First Affiliated Hospital of Chongqing Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South UniversityDepartment of Sports Medicine, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityAbstract Mitochondrial homeostasis plays a crucial role in the pathogenesis of osteoarthritis (OA), a chronic musculoskeletal disorder characterized by articular cartilage degeneration and chondrocyte apoptosis. However, molecular mechanisms underlying the association between mitophagy and OA remain unclear. Here, we aimed to investigate the role of the autophagy receptor protein optineurin (OPTN) in OA, and explore the effects of dietary intervention on OA symptoms and its relationship with OPTN-mediated mitophagy. Our findings showed the downregulation of OPTN in patients with OA. Using an Optn-knockout mouse model, we demonstrated that OPTN deficiency leads to impaired mitophagy, resulting in the accumulation of damaged mitochondria, increased production of reactive oxygen species, and chondrocyte apoptosis. Furthermore, fasting prevented OA progression by activating OPTN-mediated mitophagy and maintaining mitochondrial homeostasis in mice. The present study revealed a novel mechanism by which OPTN-mediated mitophagy influences chondrocytes and the OA phenotype in Optn-knockout mice, suggesting that OPTN-mediated mitophagy plays a crucial role in OA development and progression. This study provides new insights into the pathogenesis of OA and offers a potential avenue for the development of novel drugs targeting OPTN to mitigate OA progression.https://doi.org/10.1038/s42003-025-07541-x |
| spellingShingle | Min-Na Zhang Ran Duan Gui-Hong Chen Mei-Jun Chen Chun-Gu Hong Xin Wang Zhi-Lin Pang Chun-Yuan Chen Hua-Feng Liu Da Zhong Hui Xie Wen-Bao Hu Zheng-Zhao Liu Fasting activates optineurin-mediated mitophagy in chondrocytes to protect against osteoarthritis Communications Biology |
| title | Fasting activates optineurin-mediated mitophagy in chondrocytes to protect against osteoarthritis |
| title_full | Fasting activates optineurin-mediated mitophagy in chondrocytes to protect against osteoarthritis |
| title_fullStr | Fasting activates optineurin-mediated mitophagy in chondrocytes to protect against osteoarthritis |
| title_full_unstemmed | Fasting activates optineurin-mediated mitophagy in chondrocytes to protect against osteoarthritis |
| title_short | Fasting activates optineurin-mediated mitophagy in chondrocytes to protect against osteoarthritis |
| title_sort | fasting activates optineurin mediated mitophagy in chondrocytes to protect against osteoarthritis |
| url | https://doi.org/10.1038/s42003-025-07541-x |
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