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Corrigendum Open Access | 10.1172/jci.insight.168728

Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

Lucy V. Norling, Sarah E. Headland, Jesmond Dalli, Hildur H. Arnardottir, Oliver Haworth, Hefin R. Jones, Daniel Irimia, Charles N. Serhan, and Mauro Perretti

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Published February 8, 2023 - More info

Published in Volume 8, Issue 3 on February 8, 2023
JCI Insight. 2023;8(3):e168728. https://doi.org/10.1172/jci.insight.168728.
© 2023 Norling et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 8, 2023 - Version history
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Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis
Lucy V. Norling, … , Charles N. Serhan, Mauro Perretti
Lucy V. Norling, … , Charles N. Serhan, Mauro Perretti
The lipid mediator resolvin D1 attenuates arthritis severity, limits joint leukocyte infiltration, and promotes cartilage protection.
Research Article Immunology Inflammation

Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

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Abstract

Rheumatoid 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.

Authors

Lucy V. Norling, Sarah E. Headland, Jesmond Dalli, Hildur H. Arnardottir, Oliver Haworth, Hefin R. Jones, Daniel Irimia, Charles N. Serhan, Mauro Perretti

×

Original citation: JCI Insight. 2016;1(5):e85922. https://doi.org/10.1172/jci.insight.85922

Citation for this corrigendum: JCI Insight. 2023;8(3):e168728. https://doi.org/10.1172/jci.insight.168728

The authors recently became aware that representative illustrations presented in Figure 2A might be mistaken for original data. As this panel was used strictly for demonstrative purposes, it has been removed from the figure for clarity. The updated figure, figure legend, and description in the Results section are below.

The authors regret the errors.

Identification of SPM in human RA synovial fluids. We next profiled synovial fluid from human RA patients to determine the bioactive lipid mediator metabolome found within human joints (refer to Table 2 for patient demographics/treatment regimes). Using LC-MS/MS–based lipid mediator metabololipidomics, we identified mediators from all 3 major bioactive metabolomes in human synovial fluids including DHA-derived Rvs and AA-derived eicosanoids (Table 3). Similarly to murine arthritic joints, AA-derived autacoids classically associated with joint pain and inflammation were detected within the synovial effusate, including PGE2, PGD2, PGF2α, TXB2, and LTB4. In these fluids, we also identified the pathway marker for the protective lipoxin family 5,15-diHETE, as well as the D-series Rvs, RvD1, and RvD3. All of these mediators were identified in accordance with published criteria including matching RTs in LC and characteristic/diagnostic MS/MS fragmentation patterns (Figure 2). Of note, the levels of these proresolving mediators in these inflammatory exudates were detected within physiologically relevant concentrations (RvD1, ~31 pM, bioactive concentrations: 10 pM–100 nM; RvD3, ~23 pM, bioactive concentrations: 1 pM–10 nM) (refs. 8, 14, 15, and Table 3).

Identification of resolvin D1 (RvD1) and RvD3 in synovial fluids from rheumFigure 2

Identification of resolvin D1 (RvD1) and RvD3 in synovial fluids from rheumatoid arthritis (RA) patients. Lipid mediator levels were assessed following solid phase extraction by liquid chromatography tandem mass spectrometry–based (LC-MS/MS–based) metabololipidomics (see Methods for details). Accompanying MS/MS spectra utilized for identification. Refer to Table 2 for patient demographics and Table 3 for quantification of bioactive lipid mediators.

Footnotes

See the related article at Pro-resolving and cartilage-protective actions of Resolvin D1 in inflammatory arthritis.

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