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Open Access Research article

Protective role of frizzled-related protein B on matrix metalloproteinase induction in mouse chondrocytes

Carole Bougault1, Sabrina Priam1, Xavier Houard1, Audrey Pigenet1, Laure Sudre1, Rik J Lories2, Claire Jacques1 and Francis Berenbaum134*

Author Affiliations

1 INSERM UMRS 938, UPMC, Univ Paris 06, Faculté de Médecine Pierre & Marie Curie Paris VI, Hôpital Saint-Antoine, AP-HP, 184 rue du Faubourg Saint-Antoine, Paris 75012, France

2 Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Herestraat 49, Leuven B3000, Belgium

3 Department of Rheumatology, Assistance Publique – Hôpitaux de Paris, Saint-Antoine Hospital, 184 rue du Faubourg Saint-Antoine, Paris 75012, France

4 Inflammation–Immunopathology–Biotherapy Department (DHU i2B), 184 rue du Faubourg Saint-Antoine, Paris 75012, France

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Arthritis Research & Therapy 2014, 16:R137  doi:10.1186/ar4599

Published: 1 July 2014

Abstract

Introduction

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.