title: Engineered cartilage maturation regulates cytokine production and interleukin-1β response.
abstract: BACKGROUND
  Because the injured joint has an actively inflammatory environment, the survival and repair potential of cartilage grafts may be influenced by inflammatory processes. Understanding the interactions of those processes with the graft may lead to concepts for pharmacologic or surgical solutions allowing improved cartilage repair.
  
  
  OBJECTIVE
  We asked whether the maturation level of cartilaginous tissues generated in vitro by expanded human articular chondrocytes (HACs) modulate (1) the spontaneous production of cytokines and (2) the response to interleukin (IL)-1β.
  
  
  METHODS
  Twelve pellets/donor prepared with monolayer-expanded HACs (n = 6 donors) were evaluated at six different culture times for mRNA expression (n = 72) and spontaneous baseline release of monocyte chemoattractant protein (MCP)-1, IL-8, and transforming growth factor (TGF)-β1 (n = 72). We cultured 24 pellets/donor from each of four donors for 1 or 14 days (defined as immature and mature, respectively) and exposed the pellets to IL-1β for 3 days. MCP-1, IL-8, TGF-β1, and metalloprotease (MMP)-1 and MMP-13 were quantified in pellets and culture supernatants.
  
  
  RESULTS
  By increasing culture time, the spontaneous release of IL-8 and MCP-1 decreased (12.0- and 5.5-fold, respectively), whereas that of TGF-β1 increased (5.4-fold). As compared with immature pellets, mature pellets responded to IL-1β by releasing lower amounts of MMP-1 (2.9-fold) and MMP-13 (1.7-fold) and increased levels of IL-8, MCP-1, and TGF-β1 (1.5-, 5.0-, and 7.5-fold, respectively). IL-8 and MCP-1 promptly returned to baseline on withdrawal of IL-1β.
  
  
  CONCLUSIONS
  Our observations suggest more mature cartilaginous tissues are more resistant to IL-1β exposure and can activate chemokines required to initiate tissue repair processes.
  
  
  CONCLUSIONS
  The implantation of more mature cartilaginous tissues might provide superior graft survival and improve/accelerate cartilage repair.
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Francioli
authors.forename: Carola
authors.initials: C
authors.lastname: Cavallo
authors.forename: Brunella
authors.initials: B
authors.lastname: Grigolo
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.forename: Andrea
authors.initials: A
authors.lastname: Barbero
mesh_terms: D000328:Adult; D000368:Aged; D002358:Cartilage, Articular / Q000201:enzymology / Q000276:immunology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D019902:Chondrocytes / Q000201:enzymology / Q000276:immunology*; D020219:Chondrogenesis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D023822:Tissue Engineering; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016209:Interleukin-8; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1