Norling, Lucy V.Headland, Sarah E.Dalli, JesmondArnardottir, Hildur H.Haworth, OliverJones, Hefin R.Irimia, DanielSerhan, CharlesPerretti, Mauro2016-06-142016Norling, Lucy V., Sarah E. Headland, Jesmond Dalli, Hildur H. Arnardottir, Oliver Haworth, Hefin R. Jones, Daniel Irimia, Charles N. Serhan, and Mauro Perretti. 2016. “Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis.” JCI insight 1 (5): e85922. doi:10.1172/jci.insight.85922. http://dx.doi.org/10.1172/jci.insight.85922.2379-3708http://nrs.harvard.edu/urn-3:HUL.InstRepos:27320251Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which — once applied to human neutrophils — attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE2 biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor–deficient mice termed ALX/fpr2/3−/−. These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA.en-USJournal Article2016-06-1410.1172/jci.insight.85922