title: Adiponectin associates with markers of cartilage degradation in osteoarthritis and induces production of proinflammatory and catabolic factors through mitogen-activated protein kinase pathways.
abstract: BACKGROUND
  Adiponectin is an adipokine that regulates energy metabolism and insulin sensitivity, but recent studies have pointed also to a role in inflammation and arthritis. The purpose of the present study was to investigate the association and effects of adiponectin on inflammation and cartilage destruction in osteoarthritis (OA).
  
  
  METHODS
  Cartilage and blood samples were collected from 35 male OA patients undergoing total knee replacement surgery. Preoperative radiographs were evaluated using Ahlbäck classification criteria for knee OA. Circulating concentrations of adiponectin and biomarkers of OA, that is, cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase 3 (MMP-3), were measured. Cartilage samples obtained at the time of surgery were cultured ex vivo, and the levels of adiponectin, nitric oxide (NO), IL-6, MMP-1 and MMP-3 were determined in the culture media. In addition, the effects of adiponectin on the production of NO, IL-6, MMP-1 and MMP-3 were studied in cartilage and in primary chondrocyte cultures.
  
  
  RESULTS
  Plasma adiponectin levels and adiponectin released from OA cartilage were higher in patients with the radiologically most severe OA (Ahlbäck grades 4 and 5) than in patients with less severe disease (Ahlbäck grades 1 to 3). Plasma adiponectin concentrations correlated positively with biomarkers of OA, that is, COMP (r = 0.55, P = 0.001) and MMP-3 (r = 0.34, P = 0.046). Adiponectin was released by OA cartilage ex vivo, and it correlated positively with production of NO (r = 0.43, P = 0.012), IL-6 (r = 0.42, P = 0.018) and MMP-3 (r = 0.34, P = 0.051). Furthermore, adiponectin enhanced production of NO, IL-6, MMP-1 and MMP-3 in OA cartilage and in primary chondrocytes in vitro in a mitogen-activated protein kinase (MAPK)-dependent manner.
  
  
  CONCLUSIONS
  The findings of this study show that adiponectin is associated with, and possibly mediates, cartilage destruction in OA.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Medisiinarinkatu 3, Tampere, FI-33014, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Koskinen
authors.forename: Sami
authors.initials: S
authors.lastname: Juslin
authors.forename: Riina
authors.initials: R
authors.lastname: Nieminen
authors.forename: Teemu
authors.initials: T
authors.lastname: Moilanen
authors.forename: Katriina
authors.initials: K
authors.lastname: Vuolteenaho
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism*; D064236:Cartilage Oligomeric Matrix Protein; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000097:blood / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D064235:Matrilin Proteins; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010003:Osteoarthritis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D046509:Tissue Culture Techniques
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D005419:Flavonoids; D006023:Glycoproteins; D015850:Interleukin-6; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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