Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 Pathway
Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interl...
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2025-08-01
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| author | Tsung-Hsun Hsieh Jar-Yi Ho Chih-Chien Wang Feng-Cheng Liu Chian-Her Lee Herng-Sheng Lee Yi-Jen Peng |
| author_facet | Tsung-Hsun Hsieh Jar-Yi Ho Chih-Chien Wang Feng-Cheng Liu Chian-Her Lee Herng-Sheng Lee Yi-Jen Peng |
| author_sort | Tsung-Hsun Hsieh |
| collection | DOAJ |
| description | Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. |
| format | Article |
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| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-08-01 |
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| series | Cells |
| spelling | doaj-art-d271840dd8184c43b21b8c329fae2b0c2025-08-20T04:00:54ZengMDPI AGCells2073-44092025-08-011415120810.3390/cells14151208Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 PathwayTsung-Hsun Hsieh0Jar-Yi Ho1Chih-Chien Wang2Feng-Cheng Liu3Chian-Her Lee4Herng-Sheng Lee5Yi-Jen Peng6Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, TaiwanGraduate Institute of Life Sciences, National Defense Medical Center, Taipe 114, TaiwanDepartment of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanRheumatology/Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University Hospital, Taipei 114, TaiwanDepartment of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, TaiwanDepartment of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanIntroduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention.https://www.mdpi.com/2073-4409/14/15/1208osteoarthritismiR-22/HO-1 pathwayfucoidanchondrocytessynovial fibroblasts |
| spellingShingle | Tsung-Hsun Hsieh Jar-Yi Ho Chih-Chien Wang Feng-Cheng Liu Chian-Her Lee Herng-Sheng Lee Yi-Jen Peng Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 Pathway Cells osteoarthritis miR-22/HO-1 pathway fucoidan chondrocytes synovial fibroblasts |
| title | Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 Pathway |
| title_full | Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 Pathway |
| title_fullStr | Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 Pathway |
| title_full_unstemmed | Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 Pathway |
| title_short | Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 Pathway |
| title_sort | fucoidan modulates osteoarthritis progression through mir 22 ho 1 pathway |
| topic | osteoarthritis miR-22/HO-1 pathway fucoidan chondrocytes synovial fibroblasts |
| url | https://www.mdpi.com/2073-4409/14/15/1208 |
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