{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:47:41Z","timestamp":1790952461342,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital, Taipei City, Taiwan","doi-asserted-by":"publisher","award":["TSGH_E_113243"],"award-info":[{"award-number":["TSGH_E_113243"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital, Taipei City, Taiwan","doi-asserted-by":"publisher","award":["TSGH_C04_114042"],"award-info":[{"award-number":["TSGH_C04_114042"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital, Taipei City, Taiwan","doi-asserted-by":"publisher","award":["MND-MAB-D-113169"],"award-info":[{"award-number":["MND-MAB-D-113169"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of National Defense Medical Affairs Bureau, Republic of China","award":["TSGH_E_113243"],"award-info":[{"award-number":["TSGH_E_113243"]}]},{"name":"Ministry of National Defense Medical Affairs Bureau, Republic of China","award":["TSGH_C04_114042"],"award-info":[{"award-number":["TSGH_C04_114042"]}]},{"name":"Ministry of National Defense Medical Affairs Bureau, Republic of China","award":["MND-MAB-D-113169"],"award-info":[{"award-number":["MND-MAB-D-113169"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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-1\u03b2)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 \u03bcg\/mL fucoidan before stimulation with 1 ng\/mL of IL-1\u03b2. 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-1\u03b2-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-1\u03b2-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-1\u03b2 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.<\/jats:p>","DOI":"10.3390\/cells14151208","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T13:25:11Z","timestamp":1754486711000},"page":"1208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Fucoidan Modulates Osteoarthritis Progression Through miR-22\/HO-1 Pathway"],"prefix":"10.3390","volume":"14","author":[{"given":"Tsung-Hsun","family":"Hsieh","sequence":"first","affiliation":[{"name":"Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan"},{"name":"Department of Orthopedics and Traumatology, Taipei Veterans General Hospital, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6933-041X","authenticated-orcid":false,"given":"Jar-Yi","family":"Ho","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center, Taipe 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3709-3848","authenticated-orcid":false,"given":"Chih-Chien","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Rheumatology\/Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chian-Her","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University Hospital, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herng-Sheng","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-2103","authenticated-orcid":false,"given":"Yi-Jen","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/S0140-6736(14)60802-3","article-title":"Osteoarthritis","volume":"386","author":"Palmer","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.33590\/emj\/10313855","article-title":"Osteoarthritis-and-ageing","volume":"3","author":"Valdes","year":"2018","journal-title":"Eur. 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