title: Do arachidonic acid and its metabolites, secreted by rheumatoid and osteoarthritic synovial tissue, account for the strong inhibition of DNA synthesis in cultured human articular chondrocytes? A novel approach to the mechanism of tissue damage.
abstract: OBJECTIVE
  To further characterize factors secreted in vitro by osteoarthritic and rheumatoid arthritis synovial membranes that inhibit DNA synthesis by cultured human articular chondrocytes, and extend these findings to synovial fluid.
  
  
  METHODS
  Synovial tissue, synovial fluid and articular cartilage were obtained at surgery from two patients suffering rheumatoid arthritis and two other patients suffering from osteoarthritis. Synovial tissue was incubated in DMEM, then condition media and synovial fluids were extracted with methanol. Methanol extracts and extracted residues (hyaluronic acid, proteins) were assayed for their capacity to inhibit DNA synthesis in articular chondrocytes. Methanol extracts were also fractionated by thin layer chromatography on silica-coated plates and recovered fractions similarly tested.
  
  
  RESULTS
  All extracts exhibited strong and concentration-dependent inhibition of [3H]-thymidine incorporation. The most potent inhibition was obtained with the extracts from rheumatoid joints and the least potent inhibition was with synovial fluids. The removal of active substances with methanol leaves an inactive residue. Methanol extraction does not alter the mitogenic activity of five exogenous growth factors and two cytokines, thus suggesting that such activity is entirely due to lipids. The bulk of anti-mitotic factors extracted by methanol co-migrate when fractionated by thin layer chromatography on silica-coated plates with arachidonic acid and its lipo-oxygenase metabolites.
  
  
  CONCLUSIONS
  Inflamed synovium produces and releases lipids, most probably arachidonic acid metabolites that inhibit cell proliferation thus limiting inflammation and pannus formation in arthritis.
authors.affiliation: INSERM U-606, Hôpital Lariboisière, Paris, France, and Department of Rheumatology, University Hospital and University LA, Merida, Venezuela.
authors.forename: Gladys
authors.initials: G
authors.lastname: Colantuoni
authors.forename: Maritza
authors.initials: M
authors.lastname: Quintero
authors.forename: Andrei
authors.initials: A
authors.lastname: Panasyuk
authors.forename: Lomri
authors.initials: L
authors.lastname: Abderrahim
authors.forename: Dragoslav R
authors.initials: DR
authors.lastname: Mitrovic
mesh_terms: D000368:Aged; D016718:Arachidonic Acid / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D005260:Female; D006801:Humans; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
chemical_list: D016718:Arachidonic Acid