title: The role of resolvin D1 in the regulation of inflammatory and catabolic mediators in osteoarthritis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Université de Montréal, Montreal, QC, Canada.|Orthopedic Research Laboratory, Hôpital du Sacré-Cœur de Montréal, Room K-3045, 5400 Gouin Blvd. West, Montreal, QC, H4J 1C5, Canada.
authors.forename: Houda
authors.initials: H
authors.lastname: Benabdoune
authors.affiliation: Orthopedic Research Laboratory, Hôpital du Sacré-Cœur de Montréal, Room K-3045, 5400 Gouin Blvd. West, Montreal, QC, H4J 1C5, Canada.
authors.forename: Elsa-Patricia
authors.initials: EP
authors.lastname: Rondon
authors.affiliation: Orthopedic Research Laboratory, Hôpital du Sacré-Cœur de Montréal, Room K-3045, 5400 Gouin Blvd. West, Montreal, QC, H4J 1C5, Canada.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Orthopedic Research Laboratory, Hôpital du Sacré-Cœur de Montréal, Room K-3045, 5400 Gouin Blvd. West, Montreal, QC, H4J 1C5, Canada.
authors.forename: Julio
authors.initials: J
authors.lastname: Fernandes
authors.affiliation: Orthopedic Research Laboratory, Hôpital du Sacré-Cœur de Montréal, Room K-3045, 5400 Gouin Blvd. West, Montreal, QC, H4J 1C5, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ranger
authors.affiliation: Osteoarthritis Research Unit, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
authors.forename: Hassan
authors.initials: H
authors.lastname: Fahmi
authors.affiliation: Department of Pharmacology, Université de Montréal, Montreal, QC, Canada. mohamed.benderdour@umontreal.ca.|Orthopedic Research Laboratory, Hôpital du Sacré-Cœur de Montréal, Room K-3045, 5400 Gouin Blvd. West, Montreal, QC, H4J 1C5, Canada. mohamed.benderdour@umontreal.ca.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benderdour
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004285:Dogs; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020928:Mitogen-Activated Protein Kinases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D015232:Dinoprostone
keywords: Apoptosis; Catabolism; Inflammation; Osteoarthritis; Oxidative stress; Resolvin D1