AMPK activator decelerates osteoarthritis development by inhibition of β-catenin signaling in chondrocytes
Background: Osteoarthritis (OA) is a common degenerative joint disease with significant negative impact on the quality of life. It has been reported that abnormal upregulation of β-catenin signaling could lead to OA development; however, the upstream regulatory mechanisms of β-catenin signaling have...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Journal of Orthopaedic Translation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214031X2200105X |
| _version_ | 1797904380399190016 |
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| author | Zhenglin Zhu Yanran Huang Jun Li Dan Yi Junyi Liao Jun Xiao Guozhi Xiao Liping Tong Wei Huang Chen Di |
| author_facet | Zhenglin Zhu Yanran Huang Jun Li Dan Yi Junyi Liao Jun Xiao Guozhi Xiao Liping Tong Wei Huang Chen Di |
| author_sort | Zhenglin Zhu |
| collection | DOAJ |
| description | Background: Osteoarthritis (OA) is a common degenerative joint disease with significant negative impact on the quality of life. It has been reported that abnormal upregulation of β-catenin signaling could lead to OA development; however, the upstream regulatory mechanisms of β-catenin signaling have not been determined. Methods: Primary rat chondrocytes and ATDC5 chondrocyte cell line were stimulated with AKT2 and treated with or without metformin, an adenosine 5′-monophosphate-activated protein kinase (AMPK) activator. Westerrn blot analysis, luciferase reporter assay and immunofluorescent (IF) staining were performed to examine changes in β-cateninS552 phosphorylation and β-catenin nuclear translocation in ATDC5 cells and in primary chondrocytes. Results: We found that metformin inhibited β-cateninS552 phosphorylation in ATDC5 cells and in primary chondrocytes in a time-dependent manner. Metformin inhibited β-catenin nuclear translocation and β-catenin reporter activity. In addition, metformin also attenuated the expression of β-catenin downstream target genes. We also demonstrated that metformin inhibited β-cateninS552 phosphorylation in articular cartilage in mice. Conclusion: These findings suggest that metformin may exert its chondro-protective effect at least in part through the inhibition of β-catenin signaling in chondrocytes. The translational potential of this article: This study demonstrated the interaction between AMPK and β-catenin signaling in chondrocytes and defined novel molecular targets for the treatment of OA disease. |
| first_indexed | 2024-04-10T09:48:04Z |
| format | Article |
| id | doaj.art-bc7158c9b18343e091fdf3e8bd158d87 |
| institution | Directory Open Access Journal |
| issn | 2214-031X |
| language | English |
| last_indexed | 2024-04-10T09:48:04Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Orthopaedic Translation |
| spelling | doaj.art-bc7158c9b18343e091fdf3e8bd158d872023-02-17T04:54:25ZengElsevierJournal of Orthopaedic Translation2214-031X2023-01-0138158166AMPK activator decelerates osteoarthritis development by inhibition of β-catenin signaling in chondrocytesZhenglin Zhu0Yanran Huang1Jun Li2Dan Yi3Junyi Liao4Jun Xiao5Guozhi Xiao6Liping Tong7Wei Huang8Chen Di9Research Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, ChinaResearch Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Orthopaedic Surgery, Rush University Medical Center, Chicago, USAResearch Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, ChinaDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Orthopaedics, NanFang Hospital, Southern Medical University, Guangzhou, 510515, ChinaSchool of Medicine, Southern University of Science and Technology, Shenzhen, 518055, ChinaResearch Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Corresponding author.Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Corresponding author.Research Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Corresponding author. Research Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.Background: Osteoarthritis (OA) is a common degenerative joint disease with significant negative impact on the quality of life. It has been reported that abnormal upregulation of β-catenin signaling could lead to OA development; however, the upstream regulatory mechanisms of β-catenin signaling have not been determined. Methods: Primary rat chondrocytes and ATDC5 chondrocyte cell line were stimulated with AKT2 and treated with or without metformin, an adenosine 5′-monophosphate-activated protein kinase (AMPK) activator. Westerrn blot analysis, luciferase reporter assay and immunofluorescent (IF) staining were performed to examine changes in β-cateninS552 phosphorylation and β-catenin nuclear translocation in ATDC5 cells and in primary chondrocytes. Results: We found that metformin inhibited β-cateninS552 phosphorylation in ATDC5 cells and in primary chondrocytes in a time-dependent manner. Metformin inhibited β-catenin nuclear translocation and β-catenin reporter activity. In addition, metformin also attenuated the expression of β-catenin downstream target genes. We also demonstrated that metformin inhibited β-cateninS552 phosphorylation in articular cartilage in mice. Conclusion: These findings suggest that metformin may exert its chondro-protective effect at least in part through the inhibition of β-catenin signaling in chondrocytes. The translational potential of this article: This study demonstrated the interaction between AMPK and β-catenin signaling in chondrocytes and defined novel molecular targets for the treatment of OA disease.http://www.sciencedirect.com/science/article/pii/S2214031X2200105XOsteoarthritisAMPKβ-cateninPhosphorylationMetforminChondrocyte |
| spellingShingle | Zhenglin Zhu Yanran Huang Jun Li Dan Yi Junyi Liao Jun Xiao Guozhi Xiao Liping Tong Wei Huang Chen Di AMPK activator decelerates osteoarthritis development by inhibition of β-catenin signaling in chondrocytes Journal of Orthopaedic Translation Osteoarthritis AMPK β-catenin Phosphorylation Metformin Chondrocyte |
| title | AMPK activator decelerates osteoarthritis development by inhibition of β-catenin signaling in chondrocytes |
| title_full | AMPK activator decelerates osteoarthritis development by inhibition of β-catenin signaling in chondrocytes |
| title_fullStr | AMPK activator decelerates osteoarthritis development by inhibition of β-catenin signaling in chondrocytes |
| title_full_unstemmed | AMPK activator decelerates osteoarthritis development by inhibition of β-catenin signaling in chondrocytes |
| title_short | AMPK activator decelerates osteoarthritis development by inhibition of β-catenin signaling in chondrocytes |
| title_sort | ampk activator decelerates osteoarthritis development by inhibition of β catenin signaling in chondrocytes |
| topic | Osteoarthritis AMPK β-catenin Phosphorylation Metformin Chondrocyte |
| url | http://www.sciencedirect.com/science/article/pii/S2214031X2200105X |
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