Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritis
The involvement of chondrocyte ferroptosis in the development of osteoarthritis (OA) has been observed, and Sarsasapogenin (Sar) has therapeutic promise in a variety of inflammatory diseases. This study investigates the potential influence of Sar on the mechanism of chondrocyte ferroptotic cell deat...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223015706 |
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| author | Ruihan Chen Chenting Ying Yuxuan Zou Changjian Lin Qiangchang Fu Zhihui Xiang Jiapeng Bao Weiping Chen |
| author_facet | Ruihan Chen Chenting Ying Yuxuan Zou Changjian Lin Qiangchang Fu Zhihui Xiang Jiapeng Bao Weiping Chen |
| author_sort | Ruihan Chen |
| collection | DOAJ |
| description | The involvement of chondrocyte ferroptosis in the development of osteoarthritis (OA) has been observed, and Sarsasapogenin (Sar) has therapeutic promise in a variety of inflammatory diseases. This study investigates the potential influence of Sar on the mechanism of chondrocyte ferroptotic cell death in the progression of osteoarthritic cartilage degradation. An in vivo medial meniscus destabilization (DMM)-induced OA animal model as well as an in vitro examination of chondrocytes in an OA microenvironment induced by interleukin-1β (IL-1β) exposure were employed. Histology, immunofluorescence, quantitative RT-PCR, Western blot, cell viability, and Micro-CT analysis were utilized in conjunction with gene overexpression and knockdown to evaluate the chondroprotective effects of Sar in OA progression and the role of Yes-associated protein 1 (YAP1) in Sar-induced ferroptosis resistance of chondrocytes. In this study we found Sar reduced chondrocyte ferroptosis and OA progression. And Sar-induced chondrocyte ferroptosis resistance was mediated by YAP1. Furthermore, infection of siRNA specific to YAP1 in chondrocytes reduced Sar's chondroprotective and ferroptosis-suppressing effects during OA development. The findings suggest that Sar mitigates the progression of osteoarthritis by decreasing the sensitivity of chondrocytes to ferroptosis through the promotion of YAP1, indicating that Sar has the potential to serve as a therapeutic approach for diseases associated with ferroptosis. |
| first_indexed | 2024-03-11T11:10:44Z |
| format | Article |
| id | doaj.art-946311445e034d3d8ccbc97f81271fc9 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T11:10:44Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-946311445e034d3d8ccbc97f81271fc92023-11-12T04:39:16ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01168115772Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritisRuihan Chen0Chenting Ying1Yuxuan Zou2Changjian Lin3Qiangchang Fu4Zhihui Xiang5Jiapeng Bao6Weiping Chen7Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Jie Fang Road 88, 310009 Hangzhou, ChinaDepartment of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Jie Fang Road 88, 310009 Hangzhou, ChinaDepartment of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Jie Fang Road 88, 310009 Hangzhou, ChinaDepartment of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Jie Fang Road 88, 310009 Hangzhou, ChinaDepartment of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Jie Fang Road 88, 310009 Hangzhou, ChinaDepartment of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Jie Fang Road 88, 310009 Hangzhou, ChinaCorresponding authors.; Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Jie Fang Road 88, 310009 Hangzhou, ChinaCorresponding authors.; Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Jie Fang Road 88, 310009 Hangzhou, ChinaThe involvement of chondrocyte ferroptosis in the development of osteoarthritis (OA) has been observed, and Sarsasapogenin (Sar) has therapeutic promise in a variety of inflammatory diseases. This study investigates the potential influence of Sar on the mechanism of chondrocyte ferroptotic cell death in the progression of osteoarthritic cartilage degradation. An in vivo medial meniscus destabilization (DMM)-induced OA animal model as well as an in vitro examination of chondrocytes in an OA microenvironment induced by interleukin-1β (IL-1β) exposure were employed. Histology, immunofluorescence, quantitative RT-PCR, Western blot, cell viability, and Micro-CT analysis were utilized in conjunction with gene overexpression and knockdown to evaluate the chondroprotective effects of Sar in OA progression and the role of Yes-associated protein 1 (YAP1) in Sar-induced ferroptosis resistance of chondrocytes. In this study we found Sar reduced chondrocyte ferroptosis and OA progression. And Sar-induced chondrocyte ferroptosis resistance was mediated by YAP1. Furthermore, infection of siRNA specific to YAP1 in chondrocytes reduced Sar's chondroprotective and ferroptosis-suppressing effects during OA development. The findings suggest that Sar mitigates the progression of osteoarthritis by decreasing the sensitivity of chondrocytes to ferroptosis through the promotion of YAP1, indicating that Sar has the potential to serve as a therapeutic approach for diseases associated with ferroptosis.http://www.sciencedirect.com/science/article/pii/S0753332223015706OsteoarthritisPharmacologyFerroptosisCell signalingHippo signaling pathway |
| spellingShingle | Ruihan Chen Chenting Ying Yuxuan Zou Changjian Lin Qiangchang Fu Zhihui Xiang Jiapeng Bao Weiping Chen Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritis Biomedicine & Pharmacotherapy Osteoarthritis Pharmacology Ferroptosis Cell signaling Hippo signaling pathway |
| title | Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritis |
| title_full | Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritis |
| title_fullStr | Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritis |
| title_full_unstemmed | Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritis |
| title_short | Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritis |
| title_sort | sarsasapogenin inhibits yap1 dependent chondrocyte ferroptosis to alleviate osteoarthritis |
| topic | Osteoarthritis Pharmacology Ferroptosis Cell signaling Hippo signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223015706 |
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