title: Avocado/soybean unsaponifiables prevent the inhibitory effect of osteoarthritic subchondral osteoblasts on aggrecan and type II collagen synthesis by chondrocytes.
abstract: OBJECTIVE
  To determine the effects of avocado/soybean unsaponifiables (ASU) on osteoblast-induced dysregulation of chondrocyte metabolism.
  
  
  METHODS
  Human chondrocytes were isolated from osteoarthritis (OA) cartilage and cultured in alginate beads for 4 or 10 days in the absence or presence of osteoblasts isolated from nonsclerotic (NSC) or sclerotic (SC) zones of OA subchondral bone plate in monolayer. Before co-culture, osteoblasts were incubated or not with 10 microg/ml ASU for 72 hours. Aggrecan, type II collagen, matrix metalloproteinase-3 (MMP-3) and MMP-13, tissue inhibitor of metalloproteinase (TIMP-1), transforming growth factor-beta1 (TGF-beta1) and TGF-beta3, inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA levels in chondrocytes were quantified by RT-PCR. Aggrecan, osteocalcin, TGF-beta1, interleukin 1beta (IL-1beta), and IL-6 production were assayed by immunoassays.
  
  
  RESULTS
  In co-culture, SC osteoblasts induced a significant inhibition of matrix protein production and a significant increase of MMP synthesis by chondrocytes. In contrast, SC osteoblasts did not modify TIMP-1, TGF-beta1 and TGF-beta3, iNOS, or COX-2 mRNA levels in chondrocytes. The pretreatment of SC osteoblasts with ASU fully prevented the inhibitory effects of SC osteoblasts on matrix component production, and even significantly increased type II collagen mRNA level over the control (chondrocytes alone) value. In contrast, pretreatment of SC osteoblasts with ASU did not significantly modify the expression of MMP, TIMP-1, TGF-beta1, TGF-beta3, iNOS, or COX-2 gene by chondrocytes.
  
  
  CONCLUSIONS
  ASU prevent the osteoarthritic osteoblast-induced inhibition of matrix molecule production, suggesting that this compound may promote OA cartilage repair by acting on subchondral bone osteoblasts. This finding constitutes a new mechanism of action for this compound, known for its beneficial effects on cartilage.
authors.affiliation: Bone and Cartilage Metabolism Research Unit, Institute of Pathology B23, Liège, Belgium. yhenrotin@ulg.ac.be
authors.forename: Yves E
authors.initials: YE
authors.lastname: Henrotin
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Deberg
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Crielaard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Piccardi
authors.forename: Philippe
authors.initials: P
authors.lastname: Msika
authors.forename: Christelle
authors.initials: C
authors.lastname: Sanchez
mesh_terms: D000368:Aged; D053674:Aggrecans / Q000096:biosynthesis* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D018920:Coculture Techniques; D024043:Collagen Type II / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D027421:Persea / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013025:Glycine max / Q000737:chemistry*
chemical_list: D053674:Aggrecans; D015415:Biomarkers; D024043:Collagen Type II; D010936:Plant Extracts; D012333:RNA, Messenger; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3