Journal Article

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

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

2016

Overview

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 JNK 1/2 . 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.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Allergology / Animals / Antioxidants - pharmacology / Biomedical and Life Sciences / Biomedicine / Cell Survival - drug effects / Cells, Cultured / Chondrocytes - drug effects / Chondrocytes - metabolism / Cyclooxygenase 2 - genetics / Cyclooxygenase 2 - metabolism / Dermatology / Dinoprostone - genetics / Dinoprostone - metabolism / Docosahexaenoic Acids - pharmacology / Dogs / Humans / Immunology / Matrix Metalloproteinase 13 - genetics / Matrix Metalloproteinase 13 - metabolism / Mitogen-Activated Protein Kinases - metabolism / Neurology / NF-kappa B - metabolism / Nitric Oxide - genetics / Nitric Oxide - metabolism / Nitric Oxide Synthase Type II - genetics / Nitric Oxide Synthase Type II - metabolism / Original Research Paper / Osteoarthritis - metabolism / Pharmacology/Toxicology / Rheumatology / Synovial Fluid - metabolism