title: Protective role of frizzled-related protein B on matrix metalloproteinase induction in mouse chondrocytes.
abstract: BACKGROUND
  Our objective was to investigate whether a lack of frizzled-related protein B (FrzB), an extracellular antagonist of the Wnt signaling pathways, could enhance cartilage degradation by facilitating the expression, release and activation of matrix metalloproteinases (MMPs) by chondrocytes in response to tissue-damaging stimuli.
  
  
  METHODS
  Cartilage explants from FrzB-/- and wild-type mice were challenged by excessive dynamic compression (0.5 Hz and 1 MPa for 6 hours). Load-induced glycosaminoglycan (GAG) release and MMP enzymatic activity were assessed. Interleukin-1β (IL-1β) (10, 100 and 1000 pg/mL for 24 hours) was used to stimulate primary cultures of articular chondrocytes from FrzB-/- and wild-type mice. The expression and release of MMP-3 and -13 were determined by RT-PCR, western blot and ELISA. The accumulation of β-catenin was assessed by RT-PCR and western blot.
  
  
  RESULTS
  Cartilage degradation, as revealed by a significant increase in GAG release (2.8-fold, P = 0.014) and MMP activity (4.5-fold, P = 0.014) by explants, was induced by an excessive load. Load-induced MMP activity appeared to be enhanced in FrzB-/- cartilage explants compared to wild-type (P = 0.17). IL-1β dose-dependently induced Mmp-13 and -3 gene expression and protein release by cultured chondrocytes. IL-1β-mediated increase in MMP-13 and -3 was slightly enhanced in FrzB-/- chondrocytes compared to wild-type (P = 0.05 and P = 0.10 at gene level, P = 0.17 and P = 0.10 at protein level, respectively). Analysis of Ctnn1b and Lef1 gene expression and β-catenin accumulation at protein level suggests that the enhanced catabolic response of FrzB-/- chondrocytes to IL-1β and load may be associated with an over-stimulation of the canonical Wnt/β-catenin pathway.
  
  
  CONCLUSIONS
  Our results suggest that FrzB may have a protective role on cartilage degradation and MMP induction in mouse chondrocytes by attenuating deleterious effects of the activation of the canonical Wnt/β-catenin pathway.
authors.forename: Carole
authors.initials: C
authors.lastname: Bougault
authors.forename: Sabrina
authors.initials: S
authors.lastname: Priam
authors.forename: Xavier
authors.initials: X
authors.lastname: Houard
authors.forename: Audrey
authors.initials: A
authors.lastname: Pigenet
authors.forename: Laure
authors.initials: L
authors.lastname: Sudre
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Lories
authors.forename: Claire
authors.initials: C
authors.lastname: Jacques
authors.forename: Francis
authors.initials: F
authors.lastname: Berenbaum
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000502:physiology; D000099274:Frizzled-Related Proteins
chemical_list: D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D020782:Matrix Metalloproteinases; D000099274:Frizzled-Related Proteins