title: Control of cell migration and inflammatory mediators production by CORM-2 in osteoarthritic synoviocytes.
abstract: BACKGROUND
  Osteoarthritis (OA) is the most widespread degenerative joint disease. Inflamed synovial cells contribute to the release of inflammatory and catabolic mediators during OA leading to destruction of articular tissues. We have shown previously that CO-releasing molecules exert anti-inflammatory effects in animal models and OA chondrocytes. We have studied the ability of CORM-2 to modify the migration of human OA synoviocytes and the production of chemokines and other mediators sustaining inflammatory and catabolic processes in the OA joint.
  
  
  RESULTS
  OA synoviocytes were stimulated with interleukin(IL)-1β in the absence or presence of CORM-2. Migration assay was performed using transwell chambers. Gene expression was analyzed by quantitative PCR and protein expression by Western Blot and ELISA. CORM-2 reduced the proliferation and migration of OA synoviocytes, the expression of IL-8, CCL2, CCL20, matrix metalloproteinase(MMP)-1 and MMP-3, and the production of oxidative stress. We found that CORM-2 reduced the phosphorylation of extracellular signal-regulated kinase1/2, c-Jun N-terminal kinase1/2 and to a lesser extent p38. Our results also showed that CORM-2 significantly decreased the activation of nuclear factor-κB and activator protein-1 regulating the transcription of chemokines and MMPs in OA synoviocytes.
  
  
  CONCLUSIONS
  A number of synoviocyte functions relevant in OA synovitis and articular degradation can be down-regulated by CORM-2. These results support the interest of this class of agents for the development of novel therapeutic strategies in inflammatory and degenerative conditions.
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Valencia, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: García-Arnandis
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Guillén
authors.forename: Francisco
authors.initials: F
authors.lastname: Gomar
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Castejón
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Alcaraz
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D054418:Chemokine CCL20 / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; C108355:CCL20 protein, human; D018932:Chemokine CCL2; D054418:Chemokine CCL20; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016209:Interleukin-8; D016328:NF-kappa B; D009942:Organometallic Compounds; D018808:Transcription Factor AP-1; C447082:tricarbonyldichlororuthenium (II) dimer; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D020928:Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1