title: Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients.
abstract: OBJECTIVE
  In the present study, we investigated the role of adipocytokine leptin in the pathogenesis of osteoarthritis (OA) by measuring its effects on matrix metalloproteinase (MMP) production in human OA cartilage. In addition, the correlations between leptin and MMP concentrations in synovial fluid from OA patients were studied.
  
  
  METHODS
  Cartilage tissue obtained from leftover pieces of total knee replacement surgery from patients with OA was used in the experiments. Production of collagenases MMP-1, MMP-8 and MMP-13, and stromelysin-1 (MMP-3) in the cartilage was measured by immunoassay and the signalling pathways were explored by pharmacological means. In addition, synovial fluid samples were collected from 84 OA patients undergoing knee replacement surgery. The concentrations of leptin and MMPs in synovial fluid were measured by immunoassay.
  
  
  RESULTS
  Leptin alone and in combination with IL-1β enhanced production of MMP-1, MMP-3, and MMP-13 in human OA cartilage, while MMP-8 concentrations remained undetectable. The effects of leptin on MMP-1, MMP-3 and MMP-13 production were mediated through transcription factor NF-κβ, and through protein kinase C and MAP kinase pathways. Interestingly, leptin concentrations in synovial fluid from OA patients correlated positively with MMP-3 (r=0.51, p<0.001) and MMP-1 (r=0.41, p<0.001) levels.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study to show that leptin up-regulates MMP-1 and MMP-3 production in human OA cartilage and correlates positively to MMP-1 and MMP-3 in synovial fluid from OA patients. The findings suggest that leptin has catabolic effects in OA joints by increasing MMP production in cartilage.
authors.affiliation: The Immunopharmacology Research Group, Tampere University Hospital, Tampere, Finland. anna.koskinen@uta.fi
authors.forename: Anna
authors.initials: A
authors.lastname: Koskinen
authors.forename: Katriina
authors.initials: K
authors.lastname: Vuolteenaho
authors.forename: Riina
authors.initials: R
authors.lastname: Nieminen
authors.forename: Teemu
authors.initials: T
authors.lastname: Moilanen
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
mesh_terms: D000368:Aged; D002358:Cartilage, Articular / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000201:enzymology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D013582:Synovial Fluid / Q000187:drug effects* / Q000201:enzymology
chemical_list: D020738:Leptin; D016328:NF-kappa B; D011493:Protein Kinase C; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1