title: A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes.
abstract: OBJECTIVE
  Recent studies revealed a close connection between adipose tissue, adipokines and articular degenerative inflammatory diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). The goal of this work was to investigate the activity of adiponectin in human and murine chondrocytes and to study its functional role in the modulation of nitric oxide synthase type II (NOS2). For completeness, interleukin (IL)-6, IL-1beta, matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, prostaglandin E2 (PGE2), leukotriene B4 (LTB4), tumor necrosis factor alpha (TNF)-alpha and monocyte chemoattractant protein-1 (MCP-1) accumulation have been evaluated in adiponectin-stimulated chondrocytes cell culture supernatants.
  
  
  METHODS
  Murine ATDC5 cell line, C28/I2, C20A4, TC28a2 human immortalized chondrocytes, and human cultured chondrocytes were used. Nitrite accumulation was determined by Griess reaction. Adiponectin receptors (AdipoRs) expression was evaluated by immunofluorescence microscopy and confirmed by reverse transcriptase-polymerase chain reaction. NOS2 expression was evaluated by Western blot analysis whereas cytokines, prostanoids and metalloproteinases production was evaluated by specific enzyme-linked immunosorbent assays.
  
  
  RESULTS
  Human and murine chondrocytes express functional AdipoRs. Adiponectin induces NOS2. This effect is inhibited by aminoguanidine, dexamethasone and by a selective inhibitor of phosphatidylinositol 3-kinase. In addition, adiponectin is able to increase IL-6, MMP-3, MMP-9 and MCP-1 by murine cultured chondrocytes whereas it was unable to modulate TNF-alpha, IL-1beta, MMP-2, TIMP-1, PGE2 and LTB4 release.
  
  
  CONCLUSIONS
  These results bind more closely the interactions between fat-derived adipokines and articular inflammatory diseases, and suggest that adiponectin is a novel key element in the maintenance of cartilage homeostasis which might be considered as a potential therapeutical target in joint degenerative diseases.
authors.affiliation: Santiago University Clinical Hospital, Research Laboratory 4, NeuroEndocrine Interactions in Rheumatology and Inflammatory Diseases Laboratory, Santiago de Compostela, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Lago
authors.forename: R
authors.initials: R
authors.lastname: Gomez
authors.forename: M
authors.initials: M
authors.lastname: Otero
authors.forename: F
authors.initials: F
authors.lastname: Lago
authors.forename: R
authors.initials: R
authors.lastname: Gallego
authors.forename: C
authors.initials: C
authors.lastname: Dieguez
authors.forename: J J
authors.initials: JJ
authors.lastname: Gomez-Reino
authors.forename: O
authors.initials: O
authors.lastname: Gualillo
mesh_terms: D052242:Adiponectin / Q000494:pharmacology; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D052242:Adiponectin; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D020782:Matrix Metalloproteinases