title: Adiponectin is a potential catabolic mediator in osteoarthritis cartilage.
abstract: BACKGROUND
  Adiponectin has been implicated in the pathogenesis of osteoarthritis (OA). We studied the effects of adiponectin on the OA cartilage homeostasis.
  
  
  METHODS
  Immunohistochemical analysis was performed to evaluate differential expression of adiponectin receptors (AdipoRs) in nonlesional and lesional areas of OA cartilage. Cartilage and chondrocytes from the knee joints of primary OA patients were cultured in the presence of adiponectin (0~30 μg/ml). The levels of total nitric oxide (NO), matrix metalloproteinase (MMP)-1, -3, and -13, and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in the conditioned media. The levels of inducible NO synthase (iNOS) and MMPs were determined with the quantitative real-time reverse transcription-polymerase chain reaction. The concentrations of collagenase-cleaved type II collagen neoepitope (C1-2C) were determined in the supernatant of adiponectin-stimulated OA cartilage explants. The effects of kinase and NOS inhibitors were evaluated in the adiponectin-stimulated chondrocytes.
  
  
  RESULTS
  The expression levels of both AdipoR1 and AdipoR2 were significantly higher in lesional than in nonlesional areas of OA cartilage. The increased rate of AdipoR1-positive chondrocytes was twice that of AdipoR2-positive chondrocytes when compared between nonlesional and lesional areas. Adiponectin-stimulated OA chondrocytes showed increased total NO and MMP-1, -3, and -13 levels compared with nonstimulated cells. The TIMP-1 level was not affected. The C1-2C levels were increased by adiponectin in OA cartilage explant culture. AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK) inhibitors (compound C and SP600125) significantly suppressed adiponectin-induced production of total NO and MMP-1, -3, and -13. Inducible NOS inhibitors enhanced the expression of the adiponectin-induced MMPs.
  
  
  CONCLUSIONS
  Adiponectin causes matrix degradation in OA cartilage and increases MMPs and iNOS expression via the AMPK and JNK pathways in human OA chondrocytes. The catabolic effects of adiponectin may be counteracted by NO.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea, 463-707.
authors.forename: Eun Ha
authors.initials: EH
authors.lastname: Kang
authors.forename: Yun Jong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Tae Kyun
authors.initials: TK
authors.lastname: Kim
authors.forename: Chong Bum
authors.initials: CB
authors.lastname: Chang
authors.forename: Jin-Haeng
authors.initials: JH
authors.lastname: Chung
authors.forename: Kichul
authors.initials: K
authors.lastname: Shin
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Lee
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism*; D054419:Receptors, Adiponectin / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D016207:Cytokines; D054419:Receptors, Adiponectin; D052247:Nitric Oxide Synthase Type II; D017364:Collagenases; D020782:Matrix Metalloproteinases