Orientin alleviates chondrocyte senescence and osteoarthritis by inhibiting PI3K/AKT pathway
Aims: Osteoarthritis (OA) is a common degenerative disease that leads to pain, disability, and reduced quality of life. Orientin exhibits considerable anti-inflammatory and antioxidative properties, but its role in chondrocyte senescence and OA progress has not yet been fully characterized. The aim...
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The British Editorial Society of Bone & Joint Surgery
2025-03-01
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| Series: | Bone & Joint Research |
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| Online Access: | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.143.BJR-2023-0383.R2 |
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| author | Haitao Chen Siyi Liu Junwei Xing Yinxian Wen Liaobin Chen |
| author_facet | Haitao Chen Siyi Liu Junwei Xing Yinxian Wen Liaobin Chen |
| author_sort | Haitao Chen |
| collection | DOAJ |
| description | Aims: Osteoarthritis (OA) is a common degenerative disease that leads to pain, disability, and reduced quality of life. Orientin exhibits considerable anti-inflammatory and antioxidative properties, but its role in chondrocyte senescence and OA progress has not yet been fully characterized. The aim of this study was to evaluate the protective effects of orientin on OA. Methods: The role of orientin in extracellular matrix (ECM) degradation, mitochondrial homeostasis, and chondrocyte senescence was investigated in vitro. Meanwhile, we used molecular docking, small molecular inhibitors, and RNA interference to screen and validate candidate proteins regulated by orientin. In an anterior cruciate ligament transection (ACLT) rat model, radiograph, micro-CT, and various histological examinations were applied to evaluate the therapeutic effects of orientin on OA. Results: We found that orientin inhibited ECM degradation and senescence-associated secretory phenotype (SASP) factor expression in interleukin (IL)-1β-treated chondrocytes. Additionally, orientin reduced the level of reactive oxygen species (ROS) and improved mitochondrial homeostasis. Furthermore, orientin suppressed IL-1β-induced activation of the nuclear factor kappa B (NF-κB) signalling pathway. We also found that orientin bound to phosphoinositide 3-kinase (PI3K) and inhibited NF-κB cascades via the PI3K/AKT pathway. In vivo, we demonstrated that orientin improved cartilage wear and reduced synovial inflammation and osteophyte in an ACLT rat model. Conclusion: Orientin improves mitochondrial homeostasis, inhibits chondrocyte senescence, and alleviates OA progress via the PI3K/AKT/NF-κB axis, which suggests that orientin is a potential effective therapeutic agent for OA. Cite this article: Bone Joint Res 2025;14(3):245–258. |
| format | Article |
| id | doaj-art-5c0acf1a310146b286a23b2e2d7d36a7 |
| institution | DOAJ |
| issn | 2046-3758 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | The British Editorial Society of Bone & Joint Surgery |
| record_format | Article |
| series | Bone & Joint Research |
| spelling | doaj-art-5c0acf1a310146b286a23b2e2d7d36a72025-08-20T02:51:15ZengThe British Editorial Society of Bone & Joint SurgeryBone & Joint Research2046-37582025-03-0114324525810.1302/2046-3758.143.BJR-2023-0383.R2Orientin alleviates chondrocyte senescence and osteoarthritis by inhibiting PI3K/AKT pathwayHaitao Chen0https://orcid.org/0000-0001-9937-8676Siyi Liu1Junwei Xing2Yinxian Wen3Liaobin Chen4Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDivision of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDivision of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDivision of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDivision of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaAims: Osteoarthritis (OA) is a common degenerative disease that leads to pain, disability, and reduced quality of life. Orientin exhibits considerable anti-inflammatory and antioxidative properties, but its role in chondrocyte senescence and OA progress has not yet been fully characterized. The aim of this study was to evaluate the protective effects of orientin on OA. Methods: The role of orientin in extracellular matrix (ECM) degradation, mitochondrial homeostasis, and chondrocyte senescence was investigated in vitro. Meanwhile, we used molecular docking, small molecular inhibitors, and RNA interference to screen and validate candidate proteins regulated by orientin. In an anterior cruciate ligament transection (ACLT) rat model, radiograph, micro-CT, and various histological examinations were applied to evaluate the therapeutic effects of orientin on OA. Results: We found that orientin inhibited ECM degradation and senescence-associated secretory phenotype (SASP) factor expression in interleukin (IL)-1β-treated chondrocytes. Additionally, orientin reduced the level of reactive oxygen species (ROS) and improved mitochondrial homeostasis. Furthermore, orientin suppressed IL-1β-induced activation of the nuclear factor kappa B (NF-κB) signalling pathway. We also found that orientin bound to phosphoinositide 3-kinase (PI3K) and inhibited NF-κB cascades via the PI3K/AKT pathway. In vivo, we demonstrated that orientin improved cartilage wear and reduced synovial inflammation and osteophyte in an ACLT rat model. Conclusion: Orientin improves mitochondrial homeostasis, inhibits chondrocyte senescence, and alleviates OA progress via the PI3K/AKT/NF-κB axis, which suggests that orientin is a potential effective therapeutic agent for OA. Cite this article: Bone Joint Res 2025;14(3):245–258.https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.143.BJR-2023-0383.R2osteoarthritisorientinchondrocyte senescencereactive oxygen speciespi3k/akt pathwaychondrocytesosteoarthritis (oa)rat modelinterleukinosteophytescartilagernaradiographnuclear factor kappa banterior cruciate ligament transection (aclt) |
| spellingShingle | Haitao Chen Siyi Liu Junwei Xing Yinxian Wen Liaobin Chen Orientin alleviates chondrocyte senescence and osteoarthritis by inhibiting PI3K/AKT pathway Bone & Joint Research osteoarthritis orientin chondrocyte senescence reactive oxygen species pi3k/akt pathway chondrocytes osteoarthritis (oa) rat model interleukin osteophytes cartilage rna radiograph nuclear factor kappa b anterior cruciate ligament transection (aclt) |
| title | Orientin alleviates chondrocyte senescence and osteoarthritis by inhibiting PI3K/AKT pathway |
| title_full | Orientin alleviates chondrocyte senescence and osteoarthritis by inhibiting PI3K/AKT pathway |
| title_fullStr | Orientin alleviates chondrocyte senescence and osteoarthritis by inhibiting PI3K/AKT pathway |
| title_full_unstemmed | Orientin alleviates chondrocyte senescence and osteoarthritis by inhibiting PI3K/AKT pathway |
| title_short | Orientin alleviates chondrocyte senescence and osteoarthritis by inhibiting PI3K/AKT pathway |
| title_sort | orientin alleviates chondrocyte senescence and osteoarthritis by inhibiting pi3k akt pathway |
| topic | osteoarthritis orientin chondrocyte senescence reactive oxygen species pi3k/akt pathway chondrocytes osteoarthritis (oa) rat model interleukin osteophytes cartilage rna radiograph nuclear factor kappa b anterior cruciate ligament transection (aclt) |
| url | https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.143.BJR-2023-0383.R2 |
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