{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:07Z","timestamp":1787028907247,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of SMEs and Startups","award":["RS-2024-00514237"],"award-info":[{"award-number":["RS-2024-00514237"]}]},{"award":["RS-2024-00514237"],"award-info":[{"award-number":["RS-2024-00514237"]}],"id":[{"id":"https:\/\/ror.org\/022c4zk48","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Research Foundation of Republic of Korea government","award":["RS-2024-00396026"],"award-info":[{"award-number":["RS-2024-00396026"]}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"publisher","award":["KGM1222612"],"award-info":[{"award-number":["KGM1222612"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"award":["KGM1222612"],"award-info":[{"award-number":["KGM1222612"]}],"id":[{"id":"https:\/\/ror.org\/01wpjm123","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Osteoarthritis (OA) is a chronic degenerative joint disease characterized by persistent low-grade inflammation and progressive cartilage destruction. Macrophage-driven inflammatory responses contribute to extracellular matrix (ECM) degradation and accelerate disease progression. Here, we investigated the therapeutic potential of a DHA-derived lipid mediator mixture (LM), generated via soybean lipoxygenase and composed of 17S-hydroxydocosahexaenoic acid, resolvin D5, and protectin DX (3:47:50), in regulating macrophage\u2013chondrocyte crosstalk and OA progression. LM significantly reduced IL-6, IL-1\u03b2, and TNF-\u03b1 production in lipopolysaccharide-induced THP-1 macrophages. Conditioned medium from LM-treated macrophages attenuated ECM degradation in primary chondrocytes by suppressing MMP13 and ADAMTS5 while restoring COL2A1 and ACAN expression, indicating that LM may indirectly protects ECM by modulating the inflammatory microenvironment. In parallel, LM directly protected chondrocytes against IL-1\u03b2-induced inflammatory and catabolic responses, and restored ECM homeostasis. Mechanistically, LM significantly increased SIRT1 expression and deacetylation activity, as demonstrated by reduced NF-\u03baB p65 acetylation. Both pharmacological inhibition by EX527 and siRNA-mediated SIRT1 knockdown abolished the protective effects of LM on ECM preservation. In vivo, LM oral administration alleviated cartilage destruction, improved joint structure and suppressed OA progression in a monosodium iodoacetate-induced OA model. Notably, micro-CT studies have demonstrated that LM significantly improved subchondral bone architecture, as evidenced by increased bone volume fraction and improved trabecular parameters. Histological analyses confirmed that LM attenuated inflammation and maintained cartilage integrity. Consistently, immunohistochemical findings showed reduced MMP13 expression, restoration of collagen II and aggrecan, and upregulation of SIRT1 in the LM-treated group compared to OA rats. Collectively, these findings suggest that LM mitigates OA progression by reducing inflammation, preserving ECM homeostasis, and attenuating subchondral bone deterioration.<\/jats:p>","DOI":"10.3390\/md24060209","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:53:10Z","timestamp":1781247190000},"page":"209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["DHA-Derived Lipid Mediators Attenuate Osteoarthritis by Resolving Inflammation and Protecting Cartilage in Association with the SIRT1 Signaling Pathway"],"prefix":"10.3390","volume":"24","author":[{"given":"Yan","family":"Su","sequence":"first","affiliation":[{"name":"Microbial Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1550-0078","authenticated-orcid":false,"given":"Soon Kyu","family":"Kwon","sequence":"additional","affiliation":[{"name":"Microbial Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"},{"name":"Department of Biotechnology, Jeonbuk National University, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hack Sun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjon","family":"Han","sequence":"additional","affiliation":[{"name":"Microbial Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-628X","authenticated-orcid":false,"given":"Jung-Hee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Jeonbuk National University, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Hyun","family":"Choi","sequence":"additional","affiliation":[{"name":"Microbial Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0760-9981","authenticated-orcid":false,"given":"Jeong-Woo","family":"Seo","sequence":"additional","affiliation":[{"name":"Microbial Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.joca.2005.03.004","article-title":"Osteoarthritis development in novel experimental mouse models induced by knee joint instability","volume":"13","author":"Kamekura","year":"2005","journal-title":"Osteoarthr. 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