title: Avocado/soybean unsaponifiables increase aggrecan synthesis and reduce catabolic and proinflammatory mediator production by human osteoarthritic chondrocytes.
abstract: OBJECTIVE
  To investigate the effects of avocado (A)/soybean (S) unsaponifiables on the metabolism of human osteoarthritic (OA) chondrocytes cultured in alginate beads over 12 days.
  
  
  METHODS
  Enzymatically isolated OA chondrocytes were cultured in alginate beads in a well defined culture medium for 12 days, in the presence or not of 10-10 M interleukin 1beta (IL-1beta). DNA content was measured using a fluorometric method. Production of aggrecan (AGG), stromelysin-1 (MMP-3), tissue inhibitor of metalloproteinases-1 (TIMP-1), macrophage inflammatory protein-1beta (MIP-1beta), IL-6, and IL-8 were assayed by specific enzyme amplified sensitivity immunoassays. Prostaglandin (PG) E2 was measured by a specific radioimmunoassay and nitrite by a spectrophotometric method based on the Griess reaction. A commercial avocado and soybean mixture of unsaponifiables (A1S2) and each component separately were tested in a range of 0.625 to 40.0 micro g/ml.
  
  
  RESULTS
  After 12 days' incubation, A1S2 increased AGG synthesis and accumulation in alginate beads in a dose and time dependent manner. A1S2 promoted the recovery of aggrecan synthesis after 3 days of IL-1beta treatment. A1S2 was a potent inhibitor of basal and IL-1beta stimulated MMP-3 production. The procedure also weakly reversed the inhibitory effect of IL-1beta on TIMP-1 production. A1S2 inhibited basal production of MIP-1beta, IL-6, IL-8, NO*, and PGE2 by OA chondrocytes and partially counteracted the stimulating effect of IL-1 on PGE2. Compared to avocado or soybean added separately, the mixture had a superior effect on NO* and IL-8 production.
  
  
  CONCLUSIONS
  A1S2 stimulated aggrecan production and restored aggrecan production after IL-1beta treatment. In parallel, A1S2 decreased MMP-3 production and stimulated TIMP-1 production. These results suggest A1S2 could have structure-modifying effects in OA by inhibiting cartilage degradation and promoting cartilage repair.
authors.affiliation: Bone and Cartilage Metabolism Research Unit, University Hospital, CHU Sart-Tilman, Liège, Belgium. yhenrotin@ulg.ac.be
authors.forename: Yves E
authors.initials: YE
authors.lastname: Henrotin
authors.forename: Christelle
authors.initials: C
authors.lastname: Sanchez
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Deberg
authors.forename: Nathalie
authors.initials: N
authors.lastname: Piccardi
authors.forename: Georges Bernard
authors.initials: GB
authors.lastname: Guillou
authors.forename: Philippe
authors.initials: P
authors.lastname: Msika
authors.forename: Jean-Yves L
authors.initials: JY
authors.lastname: Reginster
mesh_terms: D000328:Adult; D053674:Aggrecans; D000464:Alginates; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054407:Chemokine CCL4; D019902:Chondrocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D015232:Dinoprostone / Q000096:biosynthesis; D016326:Extracellular Matrix Proteins; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D037181:Lectins, C-Type; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D008863:Microspheres; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism*; D027421:Persea / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis*; D013025:Glycine max / Q000737:chemistry*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
chemical_list: D053674:Aggrecans; D000464:Alginates; D054407:Chemokine CCL4; D016326:Extracellular Matrix Proteins; D006603:Hexuronic Acids; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D037181:Lectins, C-Type; D019402:Macrophage Inflammatory Proteins; D010936:Plant Extracts; D011509:Proteoglycans; D019715:Tissue Inhibitor of Metalloproteinase-1; D009569:Nitric Oxide; D020723:Glucuronic Acid; D004247:DNA; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone