title: Collagenase-3 (MMP-13) deficiency protects C57BL/6 mice from antibody-induced arthritis.
abstract: BACKGROUND
  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.
authors.forename: Anjana
authors.initials: A
authors.lastname: Singh
authors.forename: Narendiran
authors.initials: N
authors.lastname: Rajasekaran
authors.forename: Bettina
authors.initials: B
authors.lastname: Hartenstein
authors.forename: Sibylle
authors.initials: S
authors.lastname: Szabowski
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Peter
authors.initials: P
authors.lastname: Angel
authors.forename: Rolf
authors.initials: R
authors.lastname: Bräuer
authors.forename: Harald
authors.initials: H
authors.lastname: Illges
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology; D053509:Matrix Metalloproteinase 13 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse