title: Biochemical effects of two different hyaluronic acid products in a co-culture model of osteoarthritis.
abstract: OBJECTIVE
  To compare the effects of two hyaluronic acid (HA) formulations on mediators of matrix turnover and inflammation in an IL-1-treated cartilage-synovium co-culture model with the aim of elucidating mechanisms by which viscosupplementation exerts beneficial effects in osteoarthritic joints.
  
  
  METHODS
  A co-culture model (100 ng/ml interleukin-1beta (IL-1beta) added to canine synovial and cartilage explants) was used to investigate the effects of HA on cartilage-synovium interactions. Three concentrations (1x, 0.5x, and 0.1x) of two commercial sources of HA (A: Synvisc [hylan G-F 20]; B: Hyalgan [sodium hyaluronate]) were used. Co-cultures without IL-1beta (negative) or with IL-1beta (positive) but neither HA product served as controls. The liquid media were collected every 3 days and explants of cartilage and synovium were collected on days 3, 6, and 20. Media and explants were analyzed histologically, biochemically, and immunohistochemically.
  
  
  RESULTS
  Glycosaminoglycan (GAG) content was measured in cartilage explants. GAG content in explants was higher in both HA groups at the beginning and the conclusion of the study compared to the IL-1beta-treated group. GAG content of the media was significantly (P<0.05) lower in the Synvisc group than all other groups early. The Hyalgan group demonstrated progressively less GAG release later in the study. The addition of Synvisc did not decrease the matrix metalloproteinase (MMP)-3 concentrations at any point. MMP-3 concentrations were significantly (P<0.05) lower among the 1x and 0.5x Hyalgan groups on day 20 compared to the IL-1beta-treated group. On day 3, prostaglandin E(2) concentrations were significantly (P<0.05) higher in the IL-1beta-treated group compared to other groups. Both HA groups had less nitric oxide production than the control groups throughout the study.
  
  
  CONCLUSIONS
  This study supports two potential mechanisms for viscosupplementation: a biosynthetic-chondroprotective mechanism, with a possible delay in onset depending on the form of HA; and an anti-inflammatory mechanism.
authors.affiliation: Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri 65211, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Greenberg
authors.forename: A
authors.initials: A
authors.lastname: Stoker
authors.forename: S
authors.initials: S
authors.lastname: Kane
authors.forename: M
authors.initials: M
authors.lastname: Cockrell
authors.forename: J L
authors.initials: JL
authors.lastname: Cook
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D018920:Coculture Techniques; D015232:Dinoprostone / Q000378:metabolism; D004285:Dogs; D006025:Glycosaminoglycans / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D009569:Nitric Oxide; D006820:Hyaluronic Acid; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone