title: The matrilin-3 VWA1 domain modulates interleukin-6 release from primary human chondrocytes.
abstract: OBJECTIVE
  We previously demonstrated the ability of matrilin-3 to modulate the gene expression profile of primary human chondrocytes (PHCs) toward a state favoring cartilage catabolism. The structure within matrilin-3 responsible for the induction of these catabolic genes is unknown. Here, we investigated the potential of matrilin-3 (MATN3) and truncated matrilin-3 proteins, in both monomeric and oligomeric form, to stimulate interleukin (IL)-6 release in PHCs.
  
  
  METHODS
  We expressed full-length matrilin-3 oligomers, matrilin-3 von Willebrand factor A (VWA) domain oligomers, matrilin-3 four epidermal growth factor (EGF) domain oligomers, matrilin-3 monomers without oligomerization domains, matrilin-3 VWA domain monomers, and matrilin-3 4EGF monomers. We then incubated PHCs in the absence or presence of full-length matrilin-3 or one of the truncated matrilin-3 proteins and finally determined the release of IL-6 in cell-culture supernatants.
  
  
  RESULTS
  The addition of full-length matrilin-3 oligomers, matrilin-3 VWA domain oligomers, and, less pronounced, matrilin-3 monomers without oligomerization domains, and matrilin-3 4EGF-oligomers to the cell-culture medium led to a significant induction of IL-6 in PHCs.
  
  
  CONCLUSIONS
  Based on recombinant expression of different matrilin-3 domains in both monomeric and oligomeric form, this work demonstrated that the VWA1 domain of matrilin-3 is primarily responsible for the induction of IL-6 release and that the oligomerization of the VWA1 domain markedly promotes its activity.
authors.affiliation: Institute for Clinical Chemistry, University of Cologne, Cologne, Germany. andreas.klatt@uk-koeln.de
authors.forename: A R
authors.initials: AR
authors.lastname: Klatt
authors.forename: B
authors.initials: B
authors.lastname: Paul-Klausch
authors.forename: G
authors.initials: G
authors.lastname: Klinger
authors.forename: U
authors.initials: U
authors.lastname: Hillebrand
authors.forename: G
authors.initials: G
authors.lastname: Kühn
authors.forename: B
authors.initials: B
authors.lastname: Kobbe
authors.forename: J H
authors.initials: JH
authors.lastname: Renno
authors.forename: W
authors.initials: W
authors.lastname: Johannis
authors.forename: M
authors.initials: M
authors.lastname: Paulsson
authors.forename: R
authors.initials: R
authors.lastname: Wagener
mesh_terms: D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D002373:Cyclic AMP Receptor Protein; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D064235:Matrilin Proteins / Q000235:genetics / Q000494:pharmacology*; D008875:Middle Aged
chemical_list: D002373:Cyclic AMP Receptor Protein; D016326:Extracellular Matrix Proteins; D015850:Interleukin-6; D064235:Matrilin Proteins; C460760:VWA1 protein, human