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

  • 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.

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Metadaten
Document Type:Article
Language:English
Author:Anjana Singh, Narendiran Rajasekaran, Bettina Hartenstein, Sibylle Szabowski, Mieczyslaw Gajda, Peter Angel, Rolf Bräuer, Harald Illges
Parent Title (English):Arthritis Res Ther. (Arthritis Research & Therapy)
Volume:15
Issue:6
First Page:R222
ISSN:1478-6354
URN:urn:nbn:de:hbz:1044-opus-10819
DOI:https://doi.org/10.1186/ar4423
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24369907
Publisher:BioMed Central
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2013/12/27
Note:
© Singh et al.; This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Tag:Ankle Joint; Articular Cartilage; Cartilage Destruction; Joint Destruction; Wild Type Mouse
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Institut für funktionale Gen-Analytik (IfGA)
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Entry in this database:2015/04/02