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The role of resolvin D1 in the regulation of inflammatory and catabolic mediators in osteoarthritis

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Abstract

Objective and design

Resolvin D1 (RvD1), an omega-3 fatty acid derivative, has shown remarkable properties in resolving inflammation, promoting tissue repair and preserving tissue integrity. In this study, we investigated RvD1 effects on major processes involved in osteoarthritis (OA) pathophysiology.

Materials and methods

Human OA chondrocytes were treated with either 1 ng/ml interleukin-1β (IL-1β) or 20 μM 4-hydroxynonenal (HNE), then treated or not with increased concentrations of RvD1 (0–10 μM). RvD1 levels were measured by enzyme immunoassay in synovial fluids from experimental dog model of OA and sham operated dogs obtained from our previous study. Cell viability was evaluated by 3-(4,5-dimethyl-thiazoyl)-2,5-diphenyl-SH-tetrazolium bromide assay. Parameters related to inflammation, catabolism and apoptosis were determined by enzyme-linked immunosorbent assay, Western blotting, and quantitative polymerase chain reaction. Glutathione (GSH) was assessed by commercial kit. The activation of mitogen-activated protein kinases and nuclear factor-kappaB (NF-κB) pathways was evaluated by Western blot.

Results

We showed that RvD1 levels were higher in synovial fluids from OA joint compared to controls. In OA human chondrocytes, we demonstrated that RvD1 was not toxic up to 10 μM and stifled IL-1β-induced cyclooxygenase 2, prostaglandin E2, inducible nitric oxide synthase, nitric oxide, and matrix metalloproteinase-13. Our study of signalling pathways revealed that RvD1 suppressed IL-1β-induced activation of NF-κB/p65, p38/MAPK and JNK1/2. Moreover, RvD1 prevented HNE-induced cell apoptosis and oxidative stress, as indicated by inactivation of caspases, inhibition of lactate dehydrogenase release, and increased levels of Bcl2 and AKT, as well as GSH.

Conclusion

This is the first in vitro study demonstrating the beneficial effect of RvD1 in OA. That RvD1 abolishing a number of factors known to be involved in OA pathogenesis renders it a clinically valuable agent in prevention of the disease.

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Acknowledgments

This study was supported Canadian Institute of Health Research grant (#IMH 131570 for Dr Mohamed Benderdour) and by the Center of Excellence for Arthroplasty Research (for Dr Mohamed Benderdour).

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Authors and Affiliations

  1. Department of Pharmacology, Université de Montréal, Montreal, QC, Canada

    Houda Benabdoune & Mohamed Benderdour

  2. Orthopedic Research Laboratory, Hôpital du Sacré-Cœur de Montréal, Room K-3045, 5400 Gouin Blvd. West, Montreal, QC, H4J 1C5, Canada

    Houda Benabdoune, Elsa-Patricia Rondon, Qin Shi, Julio Fernandes, Pierre Ranger & Mohamed Benderdour

  3. Osteoarthritis Research Unit, Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada

    Hassan Fahmi

Authors
  1. Houda Benabdoune
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  2. Elsa-Patricia Rondon
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  3. Qin Shi
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  7. Mohamed Benderdour
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Correspondence to Mohamed Benderdour.

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Benabdoune, H., Rondon, EP., Shi, Q. et al. The role of resolvin D1 in the regulation of inflammatory and catabolic mediators in osteoarthritis. Inflamm. Res. 65, 635–645 (2016). https://doi.org/10.1007/s00011-016-0946-x

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  • DOI: https://doi.org/10.1007/s00011-016-0946-x

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