{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:21:14Z","timestamp":1784647274383,"version":"3.55.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Japan Society for the Promotion of Science KAKENHI Grant","award":["19K21397"],"award-info":[{"award-number":["19K21397"]}]},{"DOI":"10.13039\/501100003790","name":"Hiroshima University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003790","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["In Vitro Cell.Dev.Biol.-Animal"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Synovitis represents the initial pathological change in osteoarthritis and contributes to its progression. Resolvin D1 (RV-D1) is a novel and endogenous docosahexaenoic acid-derived lipid mediator, which regulates the duration and magnitude of inflammation by downregulating pro-inflammatory genes and mediators. However, the effects of RV-D1 on synovitis remain unknown. The aim of the present study was to investigate the anti-inflammatory effects of RV-D1 in human fibroblast-like synoviocytes (HFLSs) and the underlying mechanisms. The expression of the HFLS formyl peptide receptor 2 (ALX\/FPR) was examined via immunocytochemical analysis. HFLSs were treated with 1\u00a0ng\/mL recombinant human interleukin-1\u03b2 (IL-1\u03b2) and RV-D1. The gene expression of interleukin-1\u03b2 (<jats:italic>IL1B<\/jats:italic>), matrix metalloproteinase 3 (<jats:italic>MMP3<\/jats:italic>), and <jats:italic>MMP13<\/jats:italic> was examined using real-time reverse transcription-polymerase chain reaction after treatment with IL-1\u03b2 and RV-D1. The effect of RV-D1 on apoptosis was examined based on fluorescence intensity. Phosphorylation of p-38, extracellular signal-regulated kinase, c-Jun N-terminal kinase, nuclear factor kappa B (NF-\u03baB), and AKT was analyzed via western blotting. ALX\/FPR staining was observed on the cell surface. RV-D1 significantly suppressed the IL-1\u03b2-induced increase in gene and protein expression of IL-1\u03b2, MMP-3, and MMP-13. Pretreatment with 100\u00a0nM RV-D1 significantly increased the fluorescence intensity compared to that in the non-treatment group. Furthermore, pretreatment with RV-D1 significantly suppressed the phosphorylation of p-38, NF-\u03baB, and AKT. Whereas WRW4, an antagonist of ALX\/ FPR2, treatment weakened the effect of RV-D1, resulting in p-38, NF-\u03baB, and AKT phosphorylation and the protein expression of MMP-13 at levels comparable to those in the IL-1\u03b2 without RV-D1. In conclusion, RV-D1 suppressed IL-1\u03b2 and MMP expression by inhibiting the phosphorylation of p-38, NF-\u03baB, and AKT in inflammation in HFLSs. RV-D1 can be used to develop treatments for osteoarthritis and other inflammatory disorders.<\/jats:p>","DOI":"10.1007\/s11626-024-01008-9","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T20:33:12Z","timestamp":1741638792000},"page":"331-339","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Resolvin D1 suppresses inflammation in human fibroblast-like synoviocytes via the p-38, NF-\u03baB, and AKT signaling pathways"],"prefix":"10.1007","volume":"61","author":[{"given":"Makoto","family":"Yanoshita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3354-6694","authenticated-orcid":false,"given":"Naoto","family":"Hirose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayuri","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Tsuboi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Kita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Tanimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"1008_CR1","first-page":"249","volume":"50","author":"A Aggarwal","year":"2004","unstructured":"Aggarwal A, Sempowski IP (2004) Hyaluronic acid injections for knee osteoarthritis. 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