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Open Access Research article

Collagenase-3 (MMP-13) deficiency protects C57BL/6 mice from antibody-induced arthritis

Anjana Singh12, Narendiran Rajasekaran13, Bettina Hartenstein4, Sibylle Szabowski4, Mieczyslaw Gajda5, Peter Angel4, Rolf Bräuer5 and Harald Illges1*

Author Affiliations

1 Department of Natural Sciences, Immunology and Cell Biology, University of Applied Sciences, von-Liebig-Straße 20, Rheinbach D-53359, Germany

2 Present address: Department of Pathology, Maastricht University (CARIM), P. Debyelaan 25, Maastricht 6229 HX, the Netherlands

3 Present address: Pediatric Immunology, CCSR Room No. 2120, 269 Campus Drive, Stanford, CA 94305, USA

4 Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Heidelberg D-69120, Germany

5 University Hospital Jena, Institute of Pathology, Ziegelmühlenweg 1, Jena D-07740, Germany

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Arthritis Research & Therapy 2013, 15:R222  doi:10.1186/ar4423

Published: 27 December 2013

Abstract

Introduction

Matrix metalloproteinases (MMPs) are important in tissue remodelling. Here we investigate the role of collagenase-3 (MMP-13) in antibody-induced arthritis.

Methods

For this study we employed the K/BxN serum-induced arthritis model. Arthritis was induced in C57BL/6 wild type (WT) and MMP-13-deficient (MMP-13–/–) mice by intraperitoneal injection of 200 μl of K/BxN serum. Arthritis was assessed by measuring the ankle swelling. During the course of the experiments, mice were sacrificed every second day for histological examination of the ankle joints. Ankle sections were evaluated histologically for infiltration of inflammatory cells, pannus tissue formation and bone/cartilage destruction. Semi-quantitative PCR was used to determine MMP-13 expression levels in ankle joints of untreated and K/BxN serum-injected mice.

Results

This study shows that MMP-13 is a regulator of inflammation. We observed increased expression of MMP-13 in ankle joints of WT mice during K/BxN serum-induced arthritis and both K/BxN serum-treated WT and MMP-13–/– mice developed progressive arthritis with a similar onset. However, MMP-13–/– mice showed significantly reduced disease over the whole arthritic period. Ankle joints of WT mice showed severe joint destruction with extensive inflammation and erosion of cartilage and bone. In contrast, MMP-13–/– mice displayed significantly decreased severity of arthritis (50% to 60%) as analyzed by clinical and histological scoring methods.

Conclusions

MMP-13 deficiency acts to suppress the local inflammatory responses. Therefore, MMP-13 has a role in the pathogenesis of arthritis, suggesting MMP-13 is a potential therapeutic target.